# ent

id: cord-005827-wjkbrfkn
type: PROTEIN
entity:
  KompIikationen nicht aus verbleibt die orale Antikoagulation mil Cumarinderivaten ZieI INR 3 0 bis 3 5 als Mittel der Wahl 61 66 Da


id: cord-005827-wjkbrfkn
type: CHEMICAL
entity:
  eines postpartalen Auftretens eines katastrophalen Antiphospholipidsyndroms gerichtet werden 56 Antiphospholipidantik6rper


id: cord-001435-ebl8yc92
type: PROTEIN
entity:
  Salmonella Haemophilus influenzae E coli Neisseria meningitides Shigella dysenteriae and Chlamydia trachomatis 24 25 26 27 28 29


id: cord-010248-ln800g5z
type: CELL_LINE
entity:
  infected human epithelioid cell lines HeLa HEP 2 virus infected lymphoblastoid neural and glial cell lines


id: cord-001566-kkaxha7d
type: ORG
entity:
  the Institute of Basic Medical Sciences of Chinese Academy of Medical Sciences Shanghai Cancer Institute


id: cord-022310-yc6xtw0s
type: DNA
entity:
  dog and cat Infectious diseases of the dog and cat Comparison of latex agglutination indirect immunofluorescent antibody


id: cord-022310-yc6xtw0s
type: DNA
entity:
  dog and cat Coccidioidomycosis in 48 cats a retrospective study 1984 1993 Experimental canine leptospirosis caused by Leptospira interrogans serovars pomona


id: cord-022310-yc6xtw0s
type: DISEASE
entity:
  vascular disease hemolytic anemia polyarthritis idiopathic effusions granulomatous meningoencephalitis granulomatous rhinitis


id: cord-022310-yc6xtw0s
type: DISEASE
entity:
  fever ecchymoses vomiting diarrhea muscle pain uveitis coughing dyspnea renal pain thrombocytopenia renal failure


id: cord-022310-yc6xtw0s
type: DISEASE
entity:
  thrombocytopenia anemia leukopenia hyperglobulinemia proteinuria polyarthritis fever uveitis lymphadenomegaly hepatosplenomegaly


id: cord-010991-fp8hljbq
type: PROTEIN
entity:
  glucosyltransferases GTFs lipoteichoic acid antigen A 29 kDa protein antigen C 70 kDa protein antigen D 13 kDa protein AgI II 190 kDa protein AgIII 39 kDa protein


id: cord-255683-2eq24jth
type: CELL_LINE
entity:
  m36F 5 TGG TTT CGC TAC CGT GGC CCA GCC GGC CCA GGT GCA GCT GGTG 3 sense m19FcR 5 GTG AGT TTT GTC GGG CCC TAG GAC GGT CAG CTT GG 3


id: cord-255683-2eq24jth
type: DISEASE
entity:
  human immunodeficiency virus type 1 envelope Influence of N linked glycans in V4 V5 region of human immunodeficiency virus type 1 glycoprotein gp160


id: cord-254531-pv55re2x
type: PROTEIN
entity:
  Helicobacter pylori Streptococcus pneumoniae Clostridium difficile Shigella flexneri Pseudomonas aeruginosa


id: cord-254531-pv55re2x
type: GGP
entity:
  glycan receptors 1 26 29 60 61 62 63 64 65 66 67 68 69 70 71 72 73 74 75 76 77 78 In addition to E coli


id: cord-254531-pv55re2x
type: SO
entity:
  glycosylation on Fc receptor interactions Determination of aberrant O glycosylation in the IgA1 hinge region


id: cord-010570-ytv7dwr0
type: PROTEIN
entity:
  antibodies 170 P aeruginosa Human gamma globulin 172 Escherichia coli Murine E5 LPS antibodies 174 Shistosoma mansoni Praziquantel Rabbit immune sera 175 Candida albicans Amphotericin B Human gamma globulin 137 Cryptococcus neoformans


id: cord-010570-ytv7dwr0
type: ORG
entity:
  The National Institute of Child Health and Human Development Intravenous Immunoglobulin Study Group Intravenous


id: cord-010578-uib9h1lb
type: GGP
entity:
  herpesviruses cytomegalovirus varicella zoster virus human herpesvirus 6 EBV early antigen nuclear antigen and VCA and herpes simplex virus 1


id: cord-010578-uib9h1lb
type: DISEASE
entity:
  herpes simplex virus 1 the respiratory viruses adenovirus respiratory syncytial virus coronavirus and parainfluenza viruses 1 2 and 3 measles virus parvovirus B19


id: cord-010680-lc1onm53
type: DISEASE
entity:
  influenza A virus hemagglutinin HA mouse IgG1 antibody 97 They demonstrated initial expression of approximately 1 μg mL anti HA antibody


id: cord-005913-1vo1o6w8
type: DNA
entity:
  nm0895 839 sha df70d7440663372067ce0e03a4879468e2fb2a58 doc_id 5913 cord_uid 1vo1o6w8 nan molec Bini 248 97 105 1995 13 Barbas C F Amberg W Somincsits


id: cord-002846-la9svzml
type: GGP
entity:
  EGFR epidermal growth factor receptor HER2 human epidermal growth factor receptor 2 Ig immunoglobulin


id: cord-002846-la9svzml
type: GGP
entity:
  CXCR4 C X C motif chemokine receptor 4 EGFR epithelial growth factor receptor EpCAM epithelial cell adhesion molecule ERBB2 erb b2 receptor tyrosine kinase 2


id: cord-257465-9yrf7ofy
type: PROTEIN
entity:
  polymerase chain reaction Phage antibodies fi lamentous phage displaying antibody variable domains Multi subunit proteins


id: cord-009446-8keu2uay
type: WORK_OF_ART
entity:
  Single Cell Droplet Microfluidic Screening for Antibodies Specifically Binding to Target Cells Active


id: cord-009446-8keu2uay
type: FAC
entity:
  Repertoire and Neutralizing Activity of Antibodies Against Hepatitis C Virus E2 Peptide in Patients with Spontaneous Resolution of Hepatitis Bioinformatic and Statistical Analysis of Adaptive Immune Repertoires


id: cord-009446-8keu2uay
type: ORG
entity:
  Computational Strategies for Dissecting the High Dimensional Complexity of Adaptive Immune Repertoires Potent


id: cord-009446-8keu2uay
type: ORG
entity:
  Humanized Mice Multi Donor Longitudinal Antibody Repertoire Sequencing Reveals the Existence of Public Antibody Clonotypes


id: cord-018840-ts2g1ux7
type: ORG
entity:
  The National Institute of Child Health and Human Development Intravenous Immunoglobulin Clinical Trial Study Group


id: cord-283826-lgyc3sro
type: ORG
entity:
  National Institute of Child Health and Human Development NICHHD Intravenous Immunoglobulin Study Group Intravenous


id: cord-283826-lgyc3sro
type: ORG
entity:
  the International Union of Immunological Societies Primary Immunodeficiency Diseases Classification Committee Population


id: cord-017070-05vlz5dn
type: PROTEIN
entity:
  amino acid residues 490 through 510 and the other one 68 to a region including residues 130 through 150


id: cord-004167-r2s0gks8
type: GGP
entity:
  placental malaria 34 39 64 68 69 70 71 72 76 Three prospective studies including one RCT 55 and two cohort studies 42 59 provided estimates for the association between


id: cord-004167-r2s0gks8
type: GGP
entity:
  placental malaria associated adhesion phenotype Selective upregulation of a single distinctly structured


id: cord-009690-kbwz7xop
type: CELL_LINE
entity:
  Cyprus S5 10 11 A negative control containing only developing solution and a positive control containing 0 5


id: cord-009690-kbwz7xop
type: WORK_OF_ART
entity:
  Towards a Dual Lateral Flow Nanobiosensor for Simultaneous Detection of Virus Genotype Specific PCR Products A Nanostructured Microfluidic Immunoassay Platform for Highly Sensitive Infectious Pathogen Detection Development


id: cord-279105-e2zjxjox
type: WORK_OF_ART
entity:
  Portable Tests Come Online to Curb Coronavirus Pandemic Statement on Point of Care Serology Testing for SARS CoV 2


id: cord-312787-j7ye7ed5
type: TAXON
entity:
  Transmissible gastroenteritis virus Swine influenza virus encephalomyocarditis virus S hyodysenteriae sarcoptic


id: cord-274756-nnm1n09a
type: DNA
entity:
  MHC HLA DQB1 03 HLA DRβ1 or HLA DPβ1 natural killer cell immunoglobulin like receptors 1 and 4 KIR3DL1


id: cord-274756-nnm1n09a
type: PROTEIN
entity:
  DDX58 DExD H box helicase 58 DNASE2 lysosomal deoxyribonuclease 2 POLA1 DNA polymerase alpha 1 subunit


id: cord-274756-nnm1n09a
type: DNA
entity:
  PSMB8 PSMB9 PSMA3 and PSM4 genes proteasome 20S subunit beta 8 subunit beta 9 subunit alpha 3 and subunit alpha 4


id: cord-274756-nnm1n09a
type: PROTEIN
entity:
  1 and AP1S3 adaptor related protein complex 1 subunit sigma 3 159 Allergy Allergic diseases can be termed complex


id: cord-274756-nnm1n09a
type: GGP
entity:
  Burkitt s lymphoma and oral genital and stomach cancers respectively 200 Therefore immunization against these pathogens offer protection not only from infection but also from cancer Therapeutic vaccines


id: cord-274756-nnm1n09a
type: DISEASE
entity:
  immunodeficiency SCID Phagocyte defects chronic granulomatous disease hyperimmunoglobulin E IgE syndrome


id: cord-016960-xhzvp35g
type: GGP
entity:
  IL 12 interferon g and IL 6 receptors inhibitors of adhesion molecules natalizumab alicaforsen and growth factors


id: cord-016960-xhzvp35g
type: DISEASE
entity:
  anaplastic large cell lymphoma Interleukin 6 and N terminal pro brain natriuretic peptide cord blood


id: cord-016966-b23o5roz
type: GGP
entity:
  TNF α TUMOR NECROSIS FACTOR α stimulate non specifically the proliferation maturation and Immune response


id: cord-009571-mygj2nd4
type: CL
entity:
  vascular proliferation 2 vascular medial hypertrophy 2 and interstitial fibrosis 3 In MCTD children and adults have similar lesions inflammatory lesions may predominate early but can occur late Immunofluorescent data suggest an immune basis for injury the late predominance of proliferative vascular lesions suggests that vascular sclerosis is a serious complication The findings of many significant histologic lesions without clinical signs or symptoms suggest that features of this multi system disease evolve slowly and that the full spectrum of MCTD is not yet known with RA and 10 normal subjects After isolation of the lymphocytes


id: cord-009571-mygj2nd4
type: ORG
entity:
  Immunologic Study of the Post Intestinal Bypass Arthritis Dermatitis Syndrome Medical Versus Surgical Management of Ischemic Necrosis of Bone in


id: cord-313312-h607itv2
type: EVENT
entity:
  the Mechanisms of Antibody Mediated Neutralization of Flavivirus Infection Implications for Vaccine Development Antibody


id: cord-015683-a9a82of4
type: DISEASE
entity:
  visceral leishmaniasis cysticercosis echinococcosis malaria schistosomiasis toxocariasis toxoplasmosis trichinosis


id: cord-048360-n9sih438
type: WORK_OF_ART
entity:
  The Transcriptome of the Intraerythrocytic Developmental Cycle of Plasmodium falciparum Crossreactive


id: cord-133453-23rfdkuw
type: PROTEIN
entity:
  R457K K458Q K458N S459F S459Y N460T I468F I468V I468T S469P T470N E471Q E471G E471D I472V A475V G476S S477G S477T S477I


id: cord-133453-23rfdkuw
type: DISEASE
entity:
  HIV 1 gp120 SARS CoV 2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor COVID 19 immunopathology and its implications for therapy Convalescent


id: cord-010088-s9tfvtao
type: CELL_LINE
entity:
  Rh D positive platelet transfusions In 47 74 patients out of this the results for post transfusion antibody


id: cord-010088-s9tfvtao
type: ORG
entity:
  American Rare Donor Program ARDP Council of Europe International Donor Panel IDP International Society of Blood Transfusion ISBT Council of Europe Japanese


id: cord-305893-2vcy0f6i
type: CHEMICAL
entity:
  2TYG Agar ampicillin plates 1 6 tryptone 1 yeast extract 0 5 Glucose 0 5 NaCl 1 5 agar 0 005 ampicillin


id: cord-268417-6eyetb5i
type: ORG
entity:
  Lonberg Holm Arch Grsamte Virusforsch Cold Spring Harbor Symp Methods Virol 5 ME Complement Mechanisms


id: cord-298910-2601n7a9
type: DNA
entity:
  5 CCGCGTGAATTCGGGGATCCATGTCTATTCTCAAGATCC 3 forward and 5 CATGGAGTCGACCTCGAGCTTGGCCAAGG GGTTTCTG 3 reverse primers


id: cord-302382-eifh95zm
type: ORG
entity:
  Biochemical and Biophysical Research Communications Development and Characterization of a Severe Acute Respiratory Syndrome Associated Coronavirus Neutralizing Human


id: cord-302382-eifh95zm
type: ORG
entity:
  the Treatment and Prevention of Coronavirus Disease Initiates Development of Recombinant Polyclonal Antibody Therapy


id: cord-309067-aemjbkfj
type: DNA
entity:
  dog and cat Canine borreliosis Elementary body agglutination for rapidly demonstrating chlamydial agglutinins


id: cord-291626-lxa8pvt3
type: DISEASE
entity:
  influenza A H1N1 virus kinetics and symptom dynamics Point of care strategy for rapid diagnosis of novel A


id: cord-021770-zn7na974
type: ORG
entity:
  The National Institute of Child Health and Human Developments Intravenous Immunoglobulin Study Group


id: cord-021770-zn7na974
type: DISEASE
entity:
  SHIV chimeric simian immunodeficiency virus expressing HIV envelope 46 Influenza virus is another mucosal pathogen


id: cord-354325-r73datur
type: WORK_OF_ART
entity:
  Guidance for Industry S6 preclinical safety evaluation of biotechnology derived pharmaceuticals Center for Biologics Evaluation and Research and Center for Drug Evaluation and Research US Food Drug Administration Points


id: cord-103255-4k13re9y
type: PROTEIN
entity:
  human serum albumin 0 020 total soluble protein human protein C 0 001 total soluble protein erythropoietin 0 003 total soluble protein


id: cord-354790-xx6imhzb
type: DISEASE
entity:
  human immunodeficiency virus HIV hepatitis B virus HBV hepatitis C virus HCV influenza virus dengue virus Ebola virus


id: cord-031060-0o9agjiq
type: ORG
entity:
  Vaccinated Humans Development of Clinical Stage Human Monoclonal Antibodies That Treat Advanced Ebola Virus Disease


id: cord-031060-0o9agjiq
type: ORG
entity:
  the Glycoprotein Receptor Binding Site Immunization Elicited Broadly Protective Antibody Reveals Ebolavirus Fusion Loop


id: cord-339879-92esdjy9
type: PROTEIN
entity:
  anti gp41 human monoclonal antibody Human immunodeficiency virus type 1 neutralizing monoclonal antibody 2F5


id: cord-339879-92esdjy9
type: PROTEIN
entity:
  NHR mimetics Cross reactive human immunodeficiency virus type 1 neutralizing human monoclonal antibody


id: cord-328935-mn8r972x
type: DNA
entity:
  influenza virus hemagglutinin gene Equine influenza virus infections an update Probiotic bacteria enhance murine


id: cord-328935-mn8r972x
type: DISEASE
entity:
  diseases of the respiratory reproductive and gastrointestinal tracts of domestic animals and poultry


id: cord-285760-y37ji92k
type: PROTEIN
entity:
  nucleocapsid protein NP V protein V phosphoprotein P matrix M protein fusion F protein small hydrophobic SH protein hemagglutininneuraminidase HN protein


id: cord-285760-y37ji92k
type: GPE
entity:
  the Russian Federation Routine Immunization Regional and Country Profiles Russian Federation Summary of Routine Immunization and Vaccine Preventable Diseases Surveillance Data


id: cord-285760-y37ji92k
type: ORG
entity:
  Routine Immunization Regional and Country Profiles Turkey Summary of Routine Immunization and Vaccine Preventable Diseases Surveillance Data


id: cord-004247-lagv3tp7
type: WORK_OF_ART
entity:
  Generates Antibody to Pneumocystis jirovecii Vaccine Induced Immunogenicity and Protection Against Pneumocystis Pneumonia


id: cord-004247-lagv3tp7
type: WORK_OF_ART
entity:
  The Role of Antibodies in the Defense Against Tuberculosis Tuberculosis Current Issues in Diagnosis and Malaria


id: cord-354137-6oe8nj1j
type: PROTEIN
entity:
  carcinoembryonic antigen CEA carbohydrate antigen 19 9 CA19 9 carcinoma antigen 125 CA125 alpha fetoprotein AFP prostate specifi c antigen PSA CA15 3


id: cord-354137-6oe8nj1j
type: GGP
entity:
  carcinoembryonic antigen CEA carbohydrate antigen 19 9 CA19 9 carcinoma antigen 125 CA125 alpha fetoprotein AFP


id: cord-355610-7xy4s483
type: PROTEIN
entity:
  mouse anti c Myc antibody Roche Alexa 488 conjugated goat anti mouse antibody Invitrogen and PE conjugated streptavidin Invitrogen


id: cord-102704-wfuzk2dp
type: PROTEIN
entity:
  monoclonal antibodies F1 46 12 and F7 1 9 Journal of 526 Wildlife Diseases Outbreak of 528 Seoul virus among rats


id: cord-269023-g21a9ik2
type: CHEMICAL
entity:
  Gormsen 1942 Drawing on this early work Max Cooper a young biologist working with Robert Good in Minnesota followed the trail of a report first published in a poultry


id: cord-282817-vtzpf2wr
type: PROTEIN
entity:
  growth factor receptor CCR chemokine CC receptor CEA carcinoembryonic antigen DOTA 1 4 7 10 tetraazacyclododecane N N 0 N 00 N 000 tetraacetic acid EGFR epidermal growth factor receptor FAP fibroblast activation protein HMWMAA


id: cord-282817-vtzpf2wr
type: PROTEIN
entity:
  growth factor receptor LTbR leukotriene b receptor MUC 1 Mucin 1 PSCA prostate stem cell antigen PSMA prostate specific membrane antigen SAP secretory aspartyl proteinase TRAIL R2 TNF


id: cord-327883-s9nbr5y8
type: DNA
entity:
  HindIII DNA fragments Jl 4 2 kbp 0 962 to 0 985 mu K 4 0 kbp 0 014 to 0 036 mu Pi 2 7 kbp 0 to 0 014 mu and P2 2 7 kbp 0 985 to 1 mu Nucleotide sequence


id: cord-327883-s9nbr5y8
type: DNA
entity:
  alpha and picornavirus superfamilies W ILG H MAIRHOFER C MARKERT and H WOLF Max v Pettenkofer Inst for Hygiene and Med Microbiology Univ D 8000 Munich


id: cord-335316-x2t5h5gu
type: ORG
entity:
  aguesia anosmia fatigue myalgia headache co morbidities respiratory cardiovascular renal diabetes autoimmune


id: cord-327629-ep28ay11
type: ORG
entity:
  Generational and Occupational Differences in Human Factors Knowledge and Awareness A Comparison Study Mission


id: cord-023354-f2ciho6o
type: PROTEIN
entity:
  HPA antibodies anti HPA 1a 30 anti HPA 1b 3 anti HPA 3a 3 anti HPA 5a 3 anti HPA 5b 50 anti HPA 15a 2


id: cord-023354-f2ciho6o
type: PROTEIN
entity:
  Coagulation factors Fibrinogen factor II factor V factor VIII c factor IX factor X factor XI Inhibitors AT III protein C protein S Fibrinolysis plasmin


id: cord-023354-f2ciho6o
type: PROTEIN
entity:
  anti c 9 anti E 3 anti JKa 1 anti D anti JKa 1 anti D anti S 3 anti D anti C 1 anti D anti C anti K 5 anti S


id: cord-023354-f2ciho6o
type: PROTEIN
entity:
  CD3 CD4 CD8 CD2 CD19 CD20 HLA DR CD3 CD4 CD3 CD8 CD16 CD56 CD3 CD16 CD56 CD3 CD16 CD56 CD3 CD16 CD56


id: cord-023354-f2ciho6o
type: CL
entity:
  red blood transfusion Metabolic complications from massive transfusion and or the manipulation of blood products


id: cord-023354-f2ciho6o
type: GGP
entity:
  Fibrinogen factor II factor V factor VIII c factor IX factor X factor XI Inhibitors AT III protein C protein S Fibrinolysis plasmin inhibitor alpha1 antitrypsin Complement CH50


id: cord-023354-f2ciho6o
type: ORG
entity:
  National Haemovigilance Coordinatoin center Center for Medical Care of Haemophiliacs Tissue typing Center Center for Prenatal


id: cord-023354-f2ciho6o
type: ORG
entity:
  K ELEZI National Institute for Transfusion Medic Skopje Medical Center Gostivar Macedonia Introduction Population


id: cord-023354-f2ciho6o
type: ORG
entity:
  D AZOICAI Blood Transfusion Center Hospital Sfantul Spiridon Institute of Hygiene University of Medicine


id: cord-023354-f2ciho6o
type: CHEMICAL
entity:
  Le HLA 3 1 2 2 1 3 1 3 3 4 1 5 2 25 6 male antigens 2 2 1 2 3 3 3 3 1 9 f e m a l e Kandidates of renal 4 3 4 4 5 4 6 4 6 5 10 8 12 8 10 7 57 43 male transplantation 1 1 2 1 2 4 3 14


id: cord-260340-dujd28gg
type: CHEMICAL
entity:
  N linked glycan at asparagine 297 N 297 of the heavy chain is essential for the structural integrity of the IgG


id: cord-328753-qwdxgk4z
type: CL
entity:
  monocytogenes serotypes 1 2a 1 2b and 4b have been isolated from a non immune library 49 A sandwich ELISA was developed using a mAb for antibody


id: cord-338517-1mxcssjj
type: WORK_OF_ART
entity:
  Lambrecht BN Hammad H Lung Dendritic Cells in Respiratory Viral Infection and Asthma From Protection to Immunopathology Dendritic


id: cord-338517-1mxcssjj
type: WORK_OF_ART
entity:
  Neutralization of Virus Infectivity by Antibodies Old Problems in New Perspectives Neutralizing Antibodies against SARS CoV 2 and Other Human Coronaviruses MERS CoV


id: cord-338517-1mxcssjj
type: WORK_OF_ART
entity:
  Severe Acute Respiratory Syndrome Coronavirus 2 Specific Antibody Responses in Coronavirus Disease Longitudinal


id: cord-338517-1mxcssjj
type: ORG
entity:
  Alteration of Electrostatic Surface Potential Enhances Affinity and Tumor Killing Properties of Anti


id: cord-338517-1mxcssjj
type: ORG
entity:
  The Immunology of Posttransplant CMV Infection Potential Effect of CMV Immunoglobulins on Distinct Components


id: cord-338517-1mxcssjj
type: WORK_OF_ART
entity:
  A Personalized Signature and Chronotherapy Based Platform for Improving the Efficacy of Sepsis Treatment


# bib

id: cord-001060-9g8rwsm1
title: Assessment of the Evolution of Cancer Treatment Therapies
author: Arruebo, Manuel
date: 2011-08-12
txt: ./txt/cord-001060-9g8rwsm1.txt
cache: ./cache/cord-001060-9g8rwsm1.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3759197/
doi: 10.3390/cancers3033279
summary:
  These therapies can be used in isolation or in combination with other cancer treatments, thereby taking advantage of their ability to target tumors (actively or passively), to respond to physical or chemical stimulation (internal or external) and to deliver therapeutic genes to the cell nuclei. Compared to conventional therapies, nanoparticles show six clear advantages in cancer treatment and/or diagnosis: (1) they can be synthesized in specific sizes and with surface characteristics to penetrate tumors by taking advantage of the enhanced permeation and retention effect (EPR) (a mechanism known as passive targeting); (2) they can be engineered to target tumor cells by surface functionalization with biomolecules that attach to tumor-specific cell markers (a mechanism known as active targeting); (3) they can be engineered to penetrate cells and physiological barriers (e.g., blood-brain barrier, blood-retinal barrier); (4) they can increase the plasma half-life of carried chemotherapeutic drugs, which are usually highly hydrophobic; (5) they can protect a therapeutic payload from biological degradation; and (6) they can be synthesized as multifunctional platforms for combined imaging and therapeutic applications (theragnostic nanoparticles).

abstract:
  Cancer therapy has been characterized throughout history by ups and downs, not only due to the ineffectiveness of treatments and side effects, but also by hope and the reality of complete remission and cure in many cases. Within the therapeutic arsenal, alongside surgery in the case of solid tumors, are the antitumor drugs and radiation that have been the treatment of choice in some instances. In recent years, immunotherapy has become an important therapeutic alternative, and is now the first choice in many cases. Nanotechnology has recently arrived on the scene, offering nanostructures as new therapeutic alternatives for controlled drug delivery, for combining imaging and treatment, applying hyperthermia, and providing directed target therapy, among others. These therapies can be applied either alone or in combination with other components (antibodies, peptides, folic acid, etc.). In addition, gene therapy is also offering promising new methods for treatment. Here, we present a review of the evolution of cancer treatments, starting with chemotherapy, surgery, radiation and immunotherapy, and moving on to the most promising cutting-edge therapies (gene therapy and nanomedicine). We offer an historical point of view that covers the arrival of these therapies to clinical practice and the market, and the promises and challenges they present.


id: cord-001074-qevosik3
author: Selvarajah, Suganya
date: 2013-09-12
txt: ./txt/cord-001074-qevosik3.txt
cache: ./cache/cord-001074-qevosik3.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3772074/
doi: 10.1371/journal.pntd.0002423
summary:
  C9 was determined to be a potent virus neutralizing antibody and a biosensor antibody binding study demonstrated it recognized residues on intact CHIKV VLPs. Shotgun mutagenesis alanine scanning of 98 percent of the residues in the E1 and E2 glycoproteins of CHIKV envelope showed that the epitope bound by C9 included amino-acid 162 in the acid-sensitive region (ASR) of the CHIKV E2 glycoprotein. The neutralizing epitope bound by C9 mapped to the acid-sensitive region (ASR) that is critical for the rearrangement of CHIKV E2 during fusion and viral entry into host cells. Therefore, C9 is a potent neutralizing antibody that can therapeutically protect wild-type neonate mice from a lethal dose of virus at 8 and 18 hours post CHIKV inoculation. This study describes the isolation and characterization of two human monoclonal antibodies, C9 and E8, from CHIKV infected and recovered individuals.

title:
  A Neutralizing Monoclonal Antibody Targeting the Acid-Sensitive Region in Chikungunya Virus E2 Protects from Disease

abstract:
  The mosquito-borne alphavirus, chikungunya virus (CHIKV), has recently reemerged, producing the largest epidemic ever recorded for this virus, with up to 6.5 million cases of acute and chronic rheumatic disease. There are currently no licensed vaccines for CHIKV and current anti-inflammatory drug treatment is often inadequate. Here we describe the isolation and characterization of two human monoclonal antibodies, C9 and E8, from CHIKV infected and recovered individuals. C9 was determined to be a potent virus neutralizing antibody and a biosensor antibody binding study demonstrated it recognized residues on intact CHIKV VLPs. Shotgun mutagenesis alanine scanning of 98 percent of the residues in the E1 and E2 glycoproteins of CHIKV envelope showed that the epitope bound by C9 included amino-acid 162 in the acid-sensitive region (ASR) of the CHIKV E2 glycoprotein. The ASR is critical for the rearrangement of CHIKV E2 during fusion and viral entry into host cells, and we predict that C9 prevents these events from occurring. When used prophylactically in a CHIKV mouse model, C9 completely protected against CHIKV viremia and arthritis. We also observed that when administered therapeutically at 8 or 18 hours post-CHIKV challenge, C9 gave 100% protection in a pathogenic mouse model. Given that targeting this novel neutralizing epitope in E2 can potently protect both in vitro and in vivo, it is likely to be an important region both for future antibody and vaccine-based interventions against CHIKV.


id: cord-001435-ebl8yc92
title: Identification of Antigenic Proteins of the Nosocomial Pathogen Klebsiella pneumoniae
author: Hoppe, Sebastian
date: 2014-10-21
txt: ./txt/cord-001435-ebl8yc92.txt
cache: ./cache/cord-001435-ebl8yc92.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4205017/
doi: 10.1371/journal.pone.0110703
summary:
  Hence, a cDNA-based expression library was constructed and screened via microarrays to detect novel antigens of Klebsiella pneumoniae, a prominent agent of nosocomial infections well-known for its extensive antibiotics resistance, especially by extended-spectrum beta-lactamases (ESBL). After specificity analysis, homology survey and 3d structural modelling, one epitope sequence GAVVALSTTFA of KPN_00363, an ion channel protein, was identified harboring specificity for K. By identifying several novel antigens and their linear epitope sites, we have paved the way for crucial future research and applications including the design of point-of-care devices, vaccine development and serological screenings for a highly relevant nosocomial pathogen. Incubation with antibodies reactive to either of those two bacterial species resulted in signal intensities in the neighbourhood of the negative control independent of sequence alterations, see Figure 11 . In contrast, the other two proteins displaying linear epitopes, KPN_00363 and KPN_00459, indicated some specificity with the antibodies tested and two linear consensus sequences could be derived, GAVVALSTTFA and GIAFGAVELFD, respectively.

abstract:
  The continuous expansion of nosocomial infections around the globe has become a precarious situation. Key challenges include mounting dissemination of multiple resistances to antibiotics, the easy transmission and the growing mortality rates of hospital-acquired bacterial diseases. Thus, new ways to rapidly detect these infections are vital. Consequently, researchers around the globe pursue innovative approaches for point-of-care devices. In many cases the specific interaction of an antigen and a corresponding antibody is pivotal. However, the knowledge about suitable antigens is lacking. The aim of this study was to identify novel antigens as specific diagnostic markers. Additionally, these proteins might be aptly used for the generation of vaccines to improve current treatment options. Hence, a cDNA-based expression library was constructed and screened via microarrays to detect novel antigens of Klebsiella pneumoniae, a prominent agent of nosocomial infections well-known for its extensive antibiotics resistance, especially by extended-spectrum beta-lactamases (ESBL). After screening 1536 clones, 14 previously unknown immunogenic proteins were identified. Subsequently, each protein was expressed in full-length and its immunodominant character examined by ELISA and microarray analyses. Consequently, six proteins were selected for epitope mapping and three thereof possessed linear epitopes. After specificity analysis, homology survey and 3d structural modelling, one epitope sequence GAVVALSTTFA of KPN_00363, an ion channel protein, was identified harboring specificity for K. pneumoniae. The remaining epitopes showed ambiguous results regarding the specificity for K. pneumoniae. The approach adopted herein has been successfully utilized to discover novel antigens of Campylobacter jejuni and Salmonella enterica antigens before. Now, we have transferred this knowledge to the key nosocomial agent, K. pneumoniae. By identifying several novel antigens and their linear epitope sites, we have paved the way for crucial future research and applications including the design of point-of-care devices, vaccine development and serological screenings for a highly relevant nosocomial pathogen.


id: cord-001566-kkaxha7d
title: Development of Monoclonal Antibodies in China: Overview and Prospects
author: Zhang, Mao-Yu
date: 2015-02-25
txt: ./txt/cord-001566-kkaxha7d.txt
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extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4355554/
doi: 10.1155/2015/168935
summary:
  This paper aims to provide a comprehensive review of mAbs development in China through systematic analysis of drug registry, patent applications, clinical trials, academic publication, and ongoing R&D projects. Over the past three decades, monoclonal antibodies (mAbs) have achieved a dramatic development from scientific tools to powerful human therapeutic agents [1] (see Figure 1 ). Development of this class of therapeutic agents started as early as 1980s but achieved no clinical or commercial success until 2002 when adalimumab became the first human mAb approved by the US Food and Drug Administration (FDA) [14] . R&D of mAbs in China began in the 1980s [16] and the first mAb therapeutic agent (Murine Monoclonal Antibody against Human CD3 Antigen of T Lymphocyte for Injection) was introduced in 1999 [17] . This paper aims to provide a comprehensive review of mAb development in China through systematic analysis of product registry, patent application, clinical trials, academic publication, and ongoing R&D projects.

abstract:
  Monoclonal antibodies (mAbs) have become increasingly important as human therapeutic agents. Yet, current research concentrates on technology itself and pays attention to developed countries. This paper aims to provide a comprehensive review of mAbs development in China through systematic analysis of drug registry, patent applications, clinical trials, academic publication, and ongoing R&D projects. The trends in therapeutic areas and industrialization process are also highlighted. Development and research trends of mAbs are analyzed to provide a future perspective of mAbs as therapeutic agents in China.


id: cord-001726-d7iwkatn
author: Henry, Kevin A.
date: 2015-08-04
txt: ./txt/cord-001726-d7iwkatn.txt
cache: ./cache/cord-001726-d7iwkatn.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4523942/
doi: 10.3389/fmicb.2015.00755
summary:
  Particular emphases are placed on: (i) the advantages of the phage as a vaccine carrier, including its high immunogenicity, relative antigenic simplicity and ability to activate a range of immune responses, (ii) the phage''s potential as a prophylactic and therapeutic agent for infectious and chronic diseases, (iii) the regularity of the virion major coat protein lattice, which enables a variety of bioconjugation and surface chemistry applications, particularly in nanomaterials, and (iv) the phage''s large population sizes and fast generation times, which make it an excellent model system for directed protein evolution. While in some cases the results of these studies have been promising, antibody epitope-based peptide vaccines are no longer an area of active research for several reasons: (i) in many cases, peptides incompletely or inadequately mimic epitopes on folded proteins (Irving et al., 2010 ; see below); (ii) antibodies against a single epitope may be of limited utility, especially for highly variable pathogens (Van Regenmortel, 2012); and (iii) for pathogens for which protective immune responses are generated efficiently during natural infection, peptide vaccines offer few advantages over recombinant subunit and live vector vaccines, which have become easier to produce over time.

title:
  Beyond phage display: non-traditional applications of the filamentous bacteriophage as a vaccine carrier, therapeutic biologic, and bioconjugation scaffold

abstract:
  For the past 25 years, phage display technology has been an invaluable tool for studies of protein–protein interactions. However, the inherent biological, biochemical, and biophysical properties of filamentous bacteriophage, as well as the ease of its genetic manipulation, also make it an attractive platform outside the traditional phage display canon. This review will focus on the unique properties of the filamentous bacteriophage and highlight its diverse applications in current research. Particular emphases are placed on: (i) the advantages of the phage as a vaccine carrier, including its high immunogenicity, relative antigenic simplicity and ability to activate a range of immune responses, (ii) the phage’s potential as a prophylactic and therapeutic agent for infectious and chronic diseases, (iii) the regularity of the virion major coat protein lattice, which enables a variety of bioconjugation and surface chemistry applications, particularly in nanomaterials, and (iv) the phage’s large population sizes and fast generation times, which make it an excellent model system for directed protein evolution. Despite their ubiquity in the biosphere, metagenomics work is just beginning to explore the ecology of filamentous and non-filamentous phage, and their role in the evolution of bacterial populations. Thus, the filamentous phage represents a robust, inexpensive, and versatile microorganism whose bioengineering applications continue to expand in new directions, although its limitations in some spheres impose obstacles to its widespread adoption and use.


id: cord-002153-e0zhq18g
title: Efficient Qualitative and Quantitative Determination of Antigen-induced Immune Responses
author: Yang, Danlin
date: 2016-07-29
txt: ./txt/cord-002153-e0zhq18g.txt
cache: ./cache/cord-002153-e0zhq18g.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4965583/
doi: 10.1074/jbc.m116.736660
summary:
  Our workflow consists of the following two steps: 1) the use of surface plasmon resonance to quantify antigen-specific antibodies and evaluate their apparent binding affinities, and 2) the recovery of serum IgGs using an automated small scale purification system, followed by the determination of their epitope diversity using hydrogen deuterium exchange coupled with mass spectrometry. To increase the efficiency of our therapeutic antibody generation process to achieve long term success, we developed alternative methods for assessing the quality of polyclonal antibodies in immune sera, surface plasmon resonance (SPR) 2 and hydrogen deuterium exchange (HDX) coupled with mass spectrometry. In this report, we describe the following: the method development and establishment of the detection limits of our techniques, a proof-of-concept study using sera from IL-13 immunized mice, the creation of a workflow named Quality of Antibody Response (QAR), and finally the implementation of this workflow for a therapeutic anti-B-cell activating factor (BAFF) antibody generation campaign to guide the selection of optimal animal donors for hybridoma generation.

abstract:
  To determine the effectiveness of immunization strategies used in therapeutic antibody or vaccine development, it is critical to assess the quality of immunization-induced polyclonal antibody responses. Here, we developed a workflow that uses sensitive methods to quantitatively and qualitatively assess immune responses against foreign antigens with regard to antibody binding affinity and epitope diversity. The application of such detailed assessments throughout an immunization campaign can significantly reduce the resources required to generate highly specific antibodies. Our workflow consists of the following two steps: 1) the use of surface plasmon resonance to quantify antigen-specific antibodies and evaluate their apparent binding affinities, and 2) the recovery of serum IgGs using an automated small scale purification system, followed by the determination of their epitope diversity using hydrogen deuterium exchange coupled with mass spectrometry. We showed that these methods were sensitive enough to detect antigen-specific IgGs in the nanogram/μl range and that they provided information for differentiating the antibody responses of the various immunized animals that could not be obtained by conventional methods. We also showed that this workflow can guide the selection of an animal that produces high affinity antibodies with a desired epitope coverage profile, resulting in the generation of potential therapeutic monoclonal antibody clones with desirable functional profiles. We postulate that this workflow will be an important tool in the development of effective vaccines to combat the highly sophisticated evasion mechanisms of pathogens.


id: cord-002710-e8im13go
author: Taschuk, Ryan
date: 2017-10-02
txt: ./txt/cord-002710-e8im13go.txt
cache: ./cache/cord-002710-e8im13go.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5639826/
doi: 10.1080/19336896.2017.1367083
summary:
  title: Induction of PrP(Sc)-specific systemic and mucosal immune responses in white-tailed deer with an oral vaccine for chronic wasting disease Oral immunization of white-tailed deer with hAd5:tgG-RL induced PrP(Sc)-specific systemic and mucosal antibody responses with an encouraging safety profile in terms of no adverse health effects nor prolonged vector shedding. To assess the immunogenicity of hAd5:tgG-RL white-tail deer (n D 5/group) were orally immunized and epitope-specific antibody titers in serum and feces were quantified with a peptide ELISA. These results confirm that oral delivery of a recombinant viral vector, expressing an appropriate DSE and carrier molecule, is capable of inducing both systemic and mucosal antibody responses in white-tailed deer. To determine if the antibodies induced by oral immunization retained the same PrP Sc specificity as previously characterized for the parenteral vaccine, serum from hAd5:tgG-RL vaccinated animals was assayed for PrP C reactivity by ELISA, using recombinant cervid PrP 90-231 for antibody capture.

title:
  Induction of PrP(Sc)-specific systemic and mucosal immune responses in white-tailed deer with an oral vaccine for chronic wasting disease

abstract:
  The ongoing epidemic of chronic wasting disease (CWD) within cervid populations indicates the need for novel approaches for disease management. A vaccine that either reduces susceptibility to infection or reduces shedding of prions by infected animals, or a combination of both, could be of benefit for disease control. The development of such a vaccine is challenged by the unique nature of prion diseases and the requirement for formulation and delivery in an oral format for application in wildlife settings. To address the unique nature of prions, our group targets epitopes, termed disease specific epitopes (DSEs), whose exposure for antibody binding depends on disease-associated misfolding of PrP(C) into PrP(Sc). Here, a DSE corresponding to the rigid loop (RL) region, which was immunogenic following parenteral vaccination, was translated into an oral vaccine. This vaccine consists of a replication-incompetent human adenovirus expressing a truncated rabies glycoprotein G recombinant fusion with the RL epitope (hAd5:tgG-RL). Oral immunization of white-tailed deer with hAd5:tgG-RL induced PrP(Sc)-specific systemic and mucosal antibody responses with an encouraging safety profile in terms of no adverse health effects nor prolonged vector shedding. By building upon proven strategies of formulation for wildlife vaccines, these efforts generate a particular PrP(Sc)-specific oral vaccine for CWD as well as providing a versatile platform, in terms of carrier protein and biological vector, for generation of other oral, peptide-based CWD vaccines.


id: cord-002846-la9svzml
title: Current progress in innovative engineered antibodies
author: Strohl, William R.
date: 2017-08-18
txt: ./txt/cord-002846-la9svzml.txt
cache: ./cache/cord-002846-la9svzml.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5777977/
doi: 10.1007/s13238-017-0457-8
summary:
  The second most targeted protein is CD3E, found in 32 clinical stage or approved molecules, of which 26 are T cell-redirecting bispecific antibody candidates (Table 6) . For example, 10 of them bind two soluble antigens such as IL13 and IL4 (e.g., SAR156597; NCT02345070), nine bind two receptors on the , IgG-scFv fusion, Mabtyrin (IgG with non-antibody binding scaffold "centyrin" fused to C-terminal end of heavy chains); (C) IgGs to which additional antigen combining sites have been added within the structure (e.g., two-in-one antibodies, MAT "Modular Antibody Technology" platform from F-Star); (D) Engineered antibody fragments linked by short peptide linkers which can be made into bivalent, trivalent, or tetravalent formats addressing two to three targets (e.g., bispecific T-cell engager (BiTE), Nanobody platform, dual-affinity re-targeting (DART) antibodies, "tandem antibody" structures (TandAbs)); (E) Chemically coupled IgGs. Brennan et al., 1985; Garrido et al., 1990 Innovative antibodies Mack et al., 1995; Schlereth et al., 2005; Baeuerle et al., 2008 TandAb Antibody fragmentWilliam R.

abstract:
  As of May 1, 2017, 74 antibody-based molecules have been approved by a regulatory authority in a major market. Additionally, there are 70 and 575 antibody-based molecules in phase III and phase I/II clinical trials, respectively. These total 719 antibody-based clinical stage molecules include 493 naked IgGs, 87 antibody-drug conjugates, 61 bispecific antibodies, 37 total Fc fusion proteins, 17 radioimmunoglobulins, 13 antibody fragments, and 11 immunocytokines. New uses for these antibodies are being discovered each year. For oncology, many of the exciting new approaches involve antibody modulation of T-cells. There are over 80 antibodies in clinical trials targeting T cell checkpoints, 26 T-cell-redirected bispecific antibodies, and 145 chimeric antigen receptor (CAR) cell-based candidates (all currently in phase I or II clinical trials), totaling more than 250 T cell interacting clinical stage antibody-based candidates. Finally, significant progress has been made recently on routes of delivery, including delivery of proteins across the blood-brain barrier, oral delivery to the gut, delivery to the cellular cytosol, and gene- and viral-based delivery of antibodies. Thus, there are currently at least 864 antibody-based clinical stage molecules or cells, with incredible diversity in how they are constructed and what activities they impart. These are followed by a next wave of novel molecules, approaches, and new methods and routes of delivery, demonstrating that the field of antibody-based biologics is very innovative and diverse in its approaches to fulfill their promise to treat unmet medical needs.


id: cord-003435-ke0az7nf
title: mRNA as novel technology for passive immunotherapy
author: Schlake, Thomas
date: 2018-10-17
txt: ./txt/cord-003435-ke0az7nf.txt
cache: ./cache/cord-003435-ke0az7nf.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6339677/
doi: 10.1007/s00018-018-2935-4
summary:
  Recombinant technologies further expanded the available therapies based on mAbs. In vitro antibody selection technologies like phage or ribosome display were developed to enable the generation of highly specific human mAbs out of libraries that may even be naïve for the specific antigens [31] [32] [33] [34] [35] [36] 1 Schematic illustration comparing active immunization and passive antibody immunotherapies. While T cell engineering for adoptive transfer inevitably requires the use of nucleic acids encoding a target-specific receptor, antibody immunotherapy can deploy recombinant proteins. However, the effects of mRNA modifications on translation, immunostimulation and resulting protein expression appear to be variable, for instance dependent on the type of target cells. In comparison to a single transfer of cells with retroviral CAR expression, an mRNA-encoded receptor required three consecutive lymphocyte infusions to obtain a comparable antitumor effect [262] .

abstract:
  While active immunization elicits a lasting immune response by the body, passive immunotherapy transiently equips the body with exogenously generated immunological effectors in the form of either target-specific antibodies or lymphocytes functionalized with target-specific receptors. In either case, administration or expression of recombinant proteins plays a fundamental role. mRNA prepared by in vitro transcription (IVT) is increasingly appreciated as a drug substance for delivery of recombinant proteins. With its biological role as transient carrier of genetic information translated into protein in the cytoplasm, therapeutic application of mRNA combines several advantages. For example, compared to transfected DNA, mRNA harbors inherent safety features. It is not associated with the risk of inducing genomic changes and potential adverse effects are only temporary due to its transient nature. Compared to the administration of recombinant proteins produced in bioreactors, mRNA allows supplying proteins that are difficult to manufacture and offers extended pharmacokinetics for short-lived proteins. Based on great progress in understanding and manipulating mRNA properties, efficacy data in various models have now demonstrated that IVT mRNA constitutes a potent and flexible platform technology. Starting with an introduction into passive immunotherapy, this review summarizes the current status of IVT mRNA technology and its application to such immunological interventions.


id: cord-004167-r2s0gks8
author: Cutts, Julia C.
date: 2020-01-16
txt: ./txt/cord-004167-r2s0gks8.txt
cache: ./cache/cord-004167-r2s0gks8.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6964062/
doi: 10.1186/s12916-019-1467-6
summary:
  Antibody responses to pregnancy-specific pRBC and VAR2CSA antigens, measured at delivery, were associated with placental malaria (9 studies) and may therefore represent markers of infection, rather than correlates of protection. To summarize, evidence from studies included in narrative terms suggests that whilst high avidity Abs and anti-adhesion Abs measured at delivery may be associated with protection from placental infection [65] and reduced placental parasitaemia [38] , respectively, total IgG responses to VAR2CSA antigens and pregnancy-specific pRBC are positively associated with the presence of placental malaria [34, 39, 64, [68] [69] [70] [71] [72] 76] . Overall, the majority of estimates included in this review, and studies included in narrative terms, indicate that when measured at delivery, antibody responses to pregnancy-specific pRBC and VAR2CSA antigens are associated with the presence of placental infection and may therefore represent markers of infection, rather than correlates of protection.

title:
  Pregnancy-specific malarial immunity and risk of malaria in pregnancy and adverse birth outcomes: a systematic review

abstract:
  BACKGROUND: In endemic areas, pregnant women are highly susceptible to Plasmodium falciparum malaria characterized by the accumulation of parasitized red blood cells (pRBC) in the placenta. In subsequent pregnancies, women develop protective immunity to pregnancy-associated malaria and this has been hypothesized to be due to the acquisition of antibodies to the parasite variant surface antigen VAR2CSA. In this systematic review we provide the first synthesis of the association between antibodies to pregnancy-specific P. falciparum antigens and pregnancy and birth outcomes. METHODS: We conducted a systematic review and meta-analysis of population-based studies (published up to 07 June 2019) of pregnant women living in P. falciparum endemic areas that examined antibody responses to pregnancy-specific P. falciparum antigens and outcomes including placental malaria, low birthweight, preterm birth, peripheral parasitaemia, maternal anaemia, and severe malaria. RESULTS: We searched 6 databases and identified 33 studies (30 from Africa) that met predetermined inclusion and quality criteria: 16 studies contributed estimates in a format enabling inclusion in meta-analysis and 17 were included in narrative form only. Estimates were mostly from cross-sectional data (10 studies) and were heterogeneous in terms of magnitude and direction of effect. Included studies varied in terms of antigens tested, methodology used to measure antibody responses, and epidemiological setting. Antibody responses to pregnancy-specific pRBC and VAR2CSA antigens, measured at delivery, were associated with placental malaria (9 studies) and may therefore represent markers of infection, rather than correlates of protection. Antibody responses to pregnancy-specific pRBC, but not recombinant VAR2CSA antigens, were associated with trends towards protection from low birthweight (5 studies). CONCLUSIONS: Whilst antibody responses to several antigens were positively associated with the presence of placental and peripheral infections, this review did not identify evidence that any specific antibody response is associated with protection from pregnancy-associated malaria across multiple populations. Further prospective cohort studies using standardized laboratory methods to examine responses to a broad range of antigens in different epidemiological settings and throughout the gestational period, will be necessary to identify and prioritize pregnancy-specific P. falciparum antigens to advance the development of vaccines and serosurveillance tools targeting pregnant women.


id: cord-004247-lagv3tp7
title: Reassessing therapeutic antibodies for neglected and tropical diseases
author: Hooft van Huijsduijnen, Rob
date: 2020-01-30
txt: ./txt/cord-004247-lagv3tp7.txt
cache: ./cache/cord-004247-lagv3tp7.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6991954/
doi: 10.1371/journal.pntd.0007860
summary:
  This mAb was protective in an in vitro, antigen-dependent, cellular cytotoxicity assay with rat macrophages or eosinophils and also in vivo during the early phase of infection Second, beyond the cell-surface proteins, schistosomes also express a large number of glycans as part of their glycoprotein and glycolipid repertoire, and an antibody response against those glycans is mounted by the infected host [80] . In addition to antibodies that directly target and inhibit the fungal pathogen, mAbs can be directed to checkpoints that control the host immune response. In addition to highlighting the potential of mAbs as therapeutics, these studies have demonstrated the diversity of inhibitory actions that mAbs can perform on cryptococcal cells, which can include opsonization and increased phagocytosis, inhibition of fungal growth, capsular polysaccharide release and biofilm formation, antibody-mediated target cleavage, and augmentation of the host response [104] [105] [106] [107] .

abstract:
  In the past two decades there has been a significant expansion in the number of new therapeutic monoclonal antibodies (mAbs) that are approved by regulators. The discovery of these new medicines has been driven primarily by new approaches in inflammatory diseases and oncology, especially in immuno-oncology. Other recent successes have included new antibodies for use in viral diseases, including HIV. The perception of very high costs associated with mAbs has led to the assumption that they play no role in prophylaxis for diseases of poverty. However, improvements in antibody-expression yields and manufacturing processes indicate this is a cost-effective option for providing protection from many types of infection that should be revisited. Recent technology developments also indicate that several months of protection could be achieved with a single dose. Moreover, new methods in B cell sorting now enable the systematic identification of high-quality antibodies from humanized mice, or patients. This Review discusses the potential for passive immunization against schistosomiasis, fungal infections, dengue, and other neglected diseases.


id: cord-005409-8mbqkzpu
title: Complement activation by recombinant adenoviruses
author: Cichon, G
date: 2002-01-24
txt: ./txt/cord-005409-8mbqkzpu.txt
cache: ./cache/cord-005409-8mbqkzpu.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7091591/
doi: 10.1038/sj.gt.3301611
summary:
  We have determined the level of C3a (the most reactive complement component) generated in isolated citrate plasma of healthy individuals after challenge with recombinant and wild-type adenoviruses in amounts corresponding to virus blood levels to be expected in patients during adenoviral gene therapy. It has been known for a long time that adenoviruses are able to induce an antibody-dependent activation of the complement system in human plasma, but the level of activation which is reached during clinical adenoviral gene therapy (especially in intravascular infusions) might have been underestimated in the past. We will show that challenge of isolated human plasma with serotype 5 adenoviruses in amounts corresponding to blood levels reached in the above-mentioned trial, generates a level of complement activation, which holds the potency to induce serious inflammatory reactions. 13 Systemic activation of the complement system, as known from patients suffering from sepsis, severe burns or injuries, could induce autodestructive inflammatory reactions, such as adult respiratory distress syndrome (ARDS) or multiple organ failure (MOF).

abstract:
  Recombinant adenoviruses are currently the most important vector system in gene therapy. Adenoviruses frequently cause upper respiratory tract infections in humans and anti-adenoviral antibodies are found in 35–70% of the population. Therefore in the majority of potential patients receiving adenoviral gene therapy, the contact of virus particles and blood will lead to the formation of antigen–antibody complexes. These complexes have the ability to induce inflammatory reactions via an activation of the complement system. We have determined the level of C3a (the most reactive complement component) generated in isolated citrate plasma of healthy individuals after challenge with recombinant and wild-type adenoviruses in amounts corresponding to virus blood levels to be expected in patients during adenoviral gene therapy. All plasma samples containing anti-adenoviral antibodies showed a substantial, dose-dependent generation of C3a. A virus plasma level of about 7.5 × 10(9) particles/ml (which was calculated to be the highest blood level reached during clinical trials in the past) induced an average release of about 3000 ng/ml C3a (baseline levels <140 ng/ml). Analyzing the nature of anti-adenoviral antibodies showed, that not only antibodies with neutralizing properties (anti-Ad5), but also non-neutralizing anti-adenoviral antibodies are capable of complement activation. This study suggests that complement activation can be ignored in local low-dose applications of recombinant adenoviruses, but warrants attention after systemic application of large viral quantities. In clinical protocols aiming at systemic virus application, measures for monitoring and controlling the complement system should be included on a regular basis.


id: cord-005827-wjkbrfkn
title: Antiphospholipidantikörpersyndrom
author: Schmidt, Rüdiger
date: 1999
txt: ./txt/cord-005827-wjkbrfkn.txt
cache: ./cache/cord-005827-wjkbrfkn.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7095803/
doi: 10.1007/bf03044707
summary:
  Other clinical manifestations associated with APA include migraine, chorea, hemolytic anemia, heart valve disease, Budd-Chiari syndrome, perpetual pancreatitic episodes, intestinal infarctions, malignant hypertension, livedo reticularis, pre-eclampsia, fetal growth retardation or catastrophic antiphospholipid syndrome. 1Kfidiger Schmidt I , Ernst-Heinrich Scheuermann ~ , Achim Viertel 1, Helmut Geiger 1 , lnge Scharrer 2 Budd-Chiari-Syndrom, rezidivierende Pankreaufiden, intestinale Apoplexie, maligne Hypertonie;Livedo reticularis, Pr~ieklampsie, fetate WachstumsverzSgenmgen oder das sogenannte,,katastrophale Antiphospholipidantik6rpersy ndrom,_ Ira Gegensatzzum ,prim~en Antiphospholipidantik6rpersyndrom''" rinden sich Lupusantikoagulanziea und An¡250 beim ,,se-kund~iren Antiphospholipidantik/Srpersyndrom" im t(ahmen ron Autoimmun-erkrankutlget1, von.Neoplasfen und Infektionen oder sind mit dem Gebrauch bestimmter Medikamente assoziiert. Other clinical manifestations associated with APA include migraine, ch0rea, hemolytic anemia, heart Valve disease, Budd-Chiari syndrome, perpemal pancreatitic episodes, intestinal infarcfions, malignant hypertension, livedo reticularis, pre-eclampsia, fetal growth retardation or catastrophic anfiphos[10] ; dieses zeigt zudem eine fa-mili~ire H~iufung [48] sowie eine Assoziation mit HLA DR.7, DR4, DQw7 und DR.w53 [75] . el al Antiphospholipid antibodies and the anti-phospholipid syndrome in systemic lupus erythematosus

abstract:
  □ BACKGROUND: Antiphospholipid antibodies comprise a family of auto-antibodies mainly characterized by the presence of the lupus anticoagulant (LA) and anticardiolipin antibodies (ACA). □ CLINICAL APPEARANCE: The antiphospholipid antibody syndrome is defined by the appearance of frequent thromboses, repeated fetal losses and thrombocytopenia. Other clinical manifestations associated with APA include migraine, chorea, hemolytic anemia, heart valve disease, Budd-Chiari syndrome, perpetual pancreatitic episodes, intestinal infarctions, malignant hypertension, livedo reticularis, pre-eclampsia, fetal growth retardation or catastrophic antiphospholipid syndrome. LA and ACA occur in a variety of clinical conditions (secondary antiphospholipid antibody syndrome, SAPS), including other autoimmune disorders, infectious diseases, neoplastic disorders, in association with the use of certain drugs or in otherwise healthy individuals (primary antiphospholipid antibody syndrome, PAPS). □ TREATMENT: Patients with thrombosis associated with APA should receive long-term anticoagulation therapy, whereas treatment of asymptomatic patients seems to be not indicated, because only approximately 10% of patients with APA may develop thrombotic complications. In patients with PAPS there is no evidence that the prophylactic administration of immunosuppressive drugs will prevent thromboembolic events.


id: cord-005913-1vo1o6w8
title: Complement-specific antibodies: Designing novel anti-inflammatories
author: Matis, Louis A.
date: 1995
txt: ./txt/cord-005913-1vo1o6w8.txt
cache: ./cache/cord-005913-1vo1o6w8.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7095943/
doi: 10.1038/nm0895-839
abstract: nan
summary:
  The complement system is composed of more than 20 serum proteins that interact in a precise series of enzymatic cleavage and membrane binding events leading to the generation of products with immunoprotective, immunoregulatory, and proinflammatory properties 12 • Complement can be activated through either of two distinct enzymatic cascades, referred to as the classical and alternative pathways (Fig. 1) . Using a monoclonal antibody specific for mouse CS, we have shown that systemic anti-CS monoclonal antibody administration efficiently inhibited complement in vivo (inhibiting serum haemolytic activity for as long as six to seven days after a single intravenous injection), and that treatment with anti-CS monoclonal antibody was therapeutically effective in two distinct models of immune complex nephritis and autoimmune disease (Y. In addition, humanized recombinant anti-CS monoclonal antibody and scFv that retain the binding affinity and complement inhibitory activity of their murine counterparts have been produced by CDR grafting (M.


id: cord-009446-8keu2uay
title: Exploiting B Cell Receptor Analyses to Inform on HIV-1 Vaccination Strategies
author: Kreer, Christoph
date: 2020-01-01
txt: ./txt/cord-009446-8keu2uay.txt
cache: ./cache/cord-009446-8keu2uay.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7157687/
doi: 10.3390/vaccines8010013
summary:
  Focusing on the development of highly potent broadly neutralizing antibodies against HIV-1, we discuss how a detailed knowledge of the human B cell repertoire may support the development of novel vaccination strategies. Indeed, the generation of optimized bait proteins [30] or native-like envelope trimers [45] were critical steps to improve the isolation of potent HIV-1 broadly neutralizing antibodies (bNAbs) by antigen-specific sorting strategies [31, [46] [47] [48] . Only a small fraction of HIV-1-infected individuals develop highly potent bNAbs and detailed analyses of B cell receptors and antibodies at a single cell level have been limited to a few dozen subjects. Thus, a detailed understanding of the naïve B cell receptor repertoire and the constantly adapting antibody response in the context of HIV-1 infection can be highly informative for vaccine design.

abstract:
  The human antibody repertoire is generated by the recombination of different gene segments as well as by processes of somatic mutation. Together these mechanisms result in a tremendous diversity of antibodies that are able to combat various pathogens including viruses and bacteria, or malignant cells. In this review, we summarize the opportunities and challenges that are associated with the analyses of the B cell receptor repertoire and the antigen-specific B cell response. We will discuss how recent advances have increased our understanding of the antibody response and how repertoire analyses can be exploited to inform on vaccine strategies, particularly against HIV-1.


id: cord-009571-mygj2nd4
author: nan
date: 2005-11-23
txt: ./txt/cord-009571-mygj2nd4.txt
cache: ./cache/cord-009571-mygj2nd4.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7159665/
doi: 10.1002/art.1780210508
abstract: nan
summary:
  Levels of Ty cells as well as total T lymphocytes were measured in 19 patients with systemic lupus erythematosus (SLE), 11 with active and 8 with inactive disease, and in 47 normal subjects. The diagnosis of GC arthritis were studied for the presence of GC antigen (AG) and anti-in all seven patients was made by typical clinical presentation, body (AB) in serum and synovial fluid by counter-positive local culture for Ngonorrhoeae (NG) , and response to treatment. A retrospective study was instituted on 10 patients in the UCLA lupus nephritis clinic in an attempt to determine the ability of three serologic indicators-specifically immune complexes (IC), anti-DNA antibodies (DNA-ab), and C3-to predict the activity of SLE renal disease as indicated by changes in 24 hour proteinuria, serum creatinine, and creatinine clearance.

title:
  Proceedings of the 42nd annual meeting of the american rheumatism association a section of the arthritis foundation june 1 & 2, 1978 new york city abstracts of papers presented


id: cord-009581-bvihkf1r
title: Virus antibody levels in systemic lupus erythematosus
author: Hurd, Eric R.
date: 2005-11-22
txt: ./txt/cord-009581-bvihkf1r.txt
cache: ./cache/cord-009581-bvihkf1r.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7159734/
doi: 10.1002/art.1780150308
summary:
  Antibody titers to a group of viral antigens have been determined in sera from patients with systemic lupus erythematosus (SLE), control groups with inflammatory diseases and normals. In a preliminary study in this laboratory (23) of viral antibody titers in patients with lupus nephritis and matched normal controls, complement fixing antibody titers were significantly elevated to a number of myxoviruses, coronavirus OC 43 and herpes simplex virus. In the present study, an attempt has been made to compare viral antibody titers in SLE with those of control groups with inflammatory diseases as well as normal individuals. However, it is possible that the tubular structures are evidence of chronic infection in S L E with a passenger virus of a type which might act as an adjuvant for the overall elevation in viral antibody titer observed.

abstract:
  Antibody titers to a group of viral antigens have been determined in sera from patients with systemic lupus erythematosus (SLE), control groups with inflammatory diseases and normals. Mean titers in SLE sera for all viruses tested were significantly greater than in four control groups, but not greater than in active tuberculosis, both by the complement‐fixation (CF) and hemagglutination‐inhibition (HI) methods. By the CF method, only measles virus showed significantly higher titers in SLE than in all control groups; by the HI method, measles antibody titers were higher in SLE than in all groups but tuberculosis. There was no correlation between antibody titers and gammaglobulin levels. The results indicated a moderate though variable overall hypereactivity in SLE to the viral antigens tested.


id: cord-009690-kbwz7xop
author: Toubanaki, Dimitra K.
date: 2020-04-16
txt: ./txt/cord-009690-kbwz7xop.txt
cache: ./cache/cord-009690-kbwz7xop.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7162894/
doi: 10.1038/s41598-020-63553-z
summary:
  title: Development of a Nanoparticle-based Lateral Flow Strip Biosensor for Visual Detection of Whole Nervous Necrosis Virus Particles The principle of viral particles detection based on lateral flow biosensor with functionalized nanoparticles is presented in Fig. 1 . Nodavirus intact particles (virions), obtained either from SSN-1 cell culture supernatants or homogenized tissue samples, are directly applied on the LFB. The sample contains the nodavirus particles (virions) and is applied on the conjugation pad next to functionalized gold nanoparticles (Au) with polyclonal anti-nodavirus antibody. Application of that conjugate on the LFB resulted in a strong signal in the control zone, confirming the successful conjugation of anti-nodavirus antibody to Au nanoparticles (Fig. 2e) . To enable on site analysis of nodavirus, we developed and optimized a paper LFB based on gold nanoparticles for easy, specific and sensitive visual detection of nodavirus viral particles (virions) in biological samples.

title:
  Development of a Nanoparticle-based Lateral Flow Strip Biosensor for Visual Detection of Whole Nervous Necrosis Virus Particles

abstract:
  Effective analysis of pathogens causing human and veterinary diseases demands rapid, specific and sensitive detection methods which can be applied in research laboratory setups and in field for routine diagnosis. Paper lateral flow biosensors (LFBs) have been established as attractive tools for such analytical applications. In the present study a prototype LFB was designed for whole particles (virions) detection of nodavirus or fish nervous necrosis virus. Nodavirus is an important threat in the aquaculture industry, causing severe economic losses and environmental problems. The LFB was based on polyclonal antibodies conjugated on gold nanoparticles for signal visualization. Brain and retinas from fish samples were homogenized, centrifuged and the supernatant was directly applied on the LFB. Formation of a red test line was indicative of nodavirus virions presence. Nodavirus visual detection was completed in short time (30 min). Key factors of the LFB development influencing the assays’ detection limit were characterized and the optimum parameters were determined, enabling increased efficiency, excluding non-specific interactions. Therefore, the proposed LFB assay consists a robust, simple, low cost and accurate method for detection of nodavirus virions in fish samples. The proposed biosensor is ideal for development of a commercial kit to be used on aquaculture facilities by fish farmers. It is anticipated that disease monitoring and environmental safety will benefit from the simplification of time consuming and costly procedures.


id: cord-010088-s9tfvtao
title: Oral Abstracts
author: nan
date: 2013-11-01
txt: ./txt/cord-010088-s9tfvtao.txt
cache: ./cache/cord-010088-s9tfvtao.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7169312/
doi: 10.1111/vox.12100_1
abstract: nan
summary:
  These include ''incorrect blood component transfused'' events, where the blood component was intended for another recipient (frequently due to errors in patient identification at the time of collection of the pre-transfusion sample, or at the time of bedside administration), or did not meet the patient''s special needs (such as a patient with a red cell antibody who did not receive the required antigen-negative unit). Methods: Eligibility criteria for inclusion in the study included the following: transfusion of Rh D positive platelets, no anti D detectable before transfusion, no previous exposure to Rh D positive blood components, and results of follow-up testing of anti-D in patients serum available. In addition, the allelic frequency of Hpdel was calculated to be 0.015 by a genetic study of a limited number of the Japanese individuals, suggesting that Hp deficiency might distribute among the Japanese population as a phenotype of serum Hp. Aims: In this report, we present the results obtained from a hemovigilance survey carried out between 1998 and 2012, in which Hp deficiency was identified among Japanese patients who had experienced nonhemolytic TRs (NHTRs), and those obtained from a screening of Hp-deficient Japanese healthy blood donors.


id: cord-010248-ln800g5z
title: Antibody-Mediated Destruction of Virus-Infected Cells
author: Sissons, J.G. Patrick
date: 2008-02-29
txt: ./txt/cord-010248-ln800g5z.txt
cache: ./cache/cord-010248-ln800g5z.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7173112/
doi: 10.1016/s0065-2776(08)60045-0
summary:
  When lz5I-1abeled IgG antibody was bound to the surface of measles virus-infected cells at the start of the culture period, under the conditions described above for antigenic modulation, about 40% of the radioactivity was still cell associated at 12 hours and nearly all was protein bound Perrin and Oldstone, 1977) . Lysis by human serum of cells infected with HSV types 1 and 2, influenza A, parainfluenza 1, 2, 3, and 4, mumps, and measles viruses was dependent on the presence in serum of IgG antibody specific for the relevant virus and of complement (reviewed by Oldstone and Lampert, 1979) . The use of this system, composed of 11 highly purified complement proteins, provided conclusive evidence that the known proteins of the alternative and membrane attack pathways with IgG antibody are sufficient for lysis of the measles virus-infected cell, without other serum factors. It is apparent that considerably more surface-bound IgG is required to induce complement-dependent lysis of virus-infected cells than is required for antigenic modulation or antibody-dependent cell-mediated cytotoxicity.

abstract:
  This chapter describes the effect of antibody on virus-infected cells with special reference to the human system. The destruction by antibody of the infected cells through the mediation of complement is described in detail based in considerable part on the contributions of the authors. Activation of the alternative pathway by the various infected cells is of special interest. The interesting effect of the antibody-dependent cell-mediated cytotoxicity (ADCC) system involving viral antigens in cell killing is also presented. Multiple additional topics are also covered, such as the effect of antibody on the expression of viral proteins both on the surface of the cell and intracellularly. Serum antibody, produced in response to virus infections, is of major importance in preventing the spread of infection by virtue of neutralizing free virus in extracellular fluids. Virus neutralization by antibody is enhanced by complement. Antibody binding to the surface of virus-infected cells can affect virus production and release in the absence of an effector system. Immunoglobulin (IgG) antibody can mediate the destruction of virus-infected cells in conjunction with complement or cytotoxic lymphocytes. In addition, at a conceptual level there is evidence to suggest that antibody may enhance and confer specificity on basic nonspecific humoral and cell-mediated defense mechanisms.


id: cord-010570-ytv7dwr0
title: Return to the Past: The Case for Antibody-Based Therapies in Infectious Diseases
author: Casadevall, Arturo
date: 1995-07-17
txt: ./txt/cord-010570-ytv7dwr0.txt
cache: ./cache/cord-010570-ytv7dwr0.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7197598/
doi: 10.1093/clinids/21.1.150
summary:
  In the preantibiotic era, passive antibody administration (serum therapy) was useful for the treatment of many infectious diseases. We briefly review the use of antibody-based therapy in the early 20th century and make the case for reintroducing passive antibody administration for the treatment ofinfectious diseases. Given the diminishing efficacy of existing antimicrobials because of widespread resistance and the difficulties of treating infections in immunosuppressed individuals, the reintroduction of antibody-based therapies is an option that should be given serious consideration. Thus, antibody therapy is still widely used in medicine, but its role in the treatment of infections is limited largely to viral and toxin neutralization and replacement therapy in patients with immunoglobulin deficiencies. In the past, serum therapy was effective against various pathogens despite the fact that immune sera contained only small amounts of specific antibody. Antibody-based therapies have traditionally been most effective in infections where viral and toxin neutralization modifies the course of the disease.

abstract:
  In the preantibiotic era, passive antibody administration (serum therapy) was useful for the treatment of many infectious diseases. The introduction of antimicrobial chemotherapy in the 1940s led to the rapid abandonment of many forms of passive antibody therapy. Chemotherapy was more effective and less toxic than antibody therapy. In this last decade of the 20th century the efficacy of antimicrobial chemotherapy is diminishing because of the rapidly escalating number of immunocompromised individuals, the emergence of new pathogens, the reemergence of old pathogens, and widespread development of resistance to antimicrobial drugs. This diminishment in the effectiveness of chemotherapy has been paralleled by advances in monoclonal antibody technology that have made feasible the generation of human antibodies. This combination of factors makes passive antibody therapy an option worthy of serious consideration. We propose that for every pathogen there exists an antibody that will modify the infection to the benefit of the host. Such antibodies are potential antimicrobial agents. Antibody-based therapies have significant advantages and disadvantages relative to standard chemotherapy. The reintroduction of antibody-based therapy would require major changes in the practices of infectious disease specialists.


id: cord-010578-uib9h1lb
title: Seroepidemiology of Chronic Fatigue Syndrome: A Case-Control Study
author: Mawle, Alison C.
date: 1995-12-17
txt: ./txt/cord-010578-uib9h1lb.txt
cache: ./cache/cord-010578-uib9h1lb.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7197952/
doi: 10.1093/clinids/21.6.1386
summary:
  We performed serological testing for a large number of infectious agents in 26 patients from Atlanta who had chronic fatigue syndrome (CFS) and in 50 controls matched by age, race, and sex. We performed serological testing for a large number of infectious agents in 26 patients from Atlanta who had chronic fatigue syndrome (CFS) and in 50 controls matched by age, race, and sex. We conducted serological tests for a large number of infectious agents as part of a case-control study assessing risk factors for CFS. Antibodies against human T-lymphotrophic virus types I and II were detected with an ELISA, and confirmatory testing was performed by western blotting [5] . All other agents tested were detected in ;;:::25% of CFS cases, and antibody levels were compared between cases and controls. Evidence for active Epstein-Barr virus infection in patients with persistent unexplained illness: elevated anti-early antigen antibodies

abstract:
  We performed serological testing for a large number of infectious agents in 26 patients from Atlanta who had chronic fatigue syndrome (CFS) and in 50 controls matched by age, race, and sex. We did not find any agent associated with CFS. In addition, we did not find elevated levels of antibody to any of a wide range of agents examined. In particular, we did not find elevated titers of antibody to any herpesvirus, nor did we find evidence of enteroviral exposure in this group of patients.


id: cord-010680-lc1onm53
title: In Vivo Delivery of Nucleic Acid-Encoded Monoclonal Antibodies
author: Patel, Ami
date: 2020-03-10
txt: ./txt/cord-010680-lc1onm53.txt
cache: ./cache/cord-010680-lc1onm53.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7211204/
doi: 10.1007/s40259-020-00412-3
summary:
  Some of these hurdles may be overcome through transient in vivo gene delivery platforms, such as non-viral synthetic plasmid DNA and messenger RNA vectors that are engineered to encode optimized mAb genes. In this review, we focus on nucleic acid delivery of antibody employing synthetic plasmid DNA vector platforms, and RNA delivery, these being important approaches that are advancing simple, rapid, in vivo expression and having an impact in animal models of infectious diseases and cancer, among others. The original studies surrounding in vivo antibody gene delivery focused primarily on gene delivery using recombinant viral vectors such as AAV and adenovirus (Ad), which were advanced clinically, building on work in the traditional gene therapy-based field. Additional studies to help evaluate fully human pDNA-mAbs in mouse models would be highly informative for both non-viral and viral delivery and provide an important path forward for preclinical evaluation of in vivo-delivered antibodies [109] .

abstract:
  Antibody immunotherapy is revolutionizing modern medicine. The field has advanced dramatically over the past 40 years, driven in part by major advances in isolation and manufacturing technologies that have brought these important biologics to the forefront of modern medicine. However, the global uptake of monoclonal antibody (mAb) biologics is impeded by biophysical and biochemical liabilities, production limitations, the need for cold-chain storage and transport, as well as high costs of manufacturing and distribution. Some of these hurdles may be overcome through transient in vivo gene delivery platforms, such as non-viral synthetic plasmid DNA and messenger RNA vectors that are engineered to encode optimized mAb genes. These approaches turn the body into a biological factory for antibody production, eliminating many of the steps involved in bioprocesses and providing several other significant advantages, and differ from traditional gene therapy (permanent delivery) approaches. In this review, we focus on nucleic acid delivery of antibody employing synthetic plasmid DNA vector platforms, and RNA delivery, these being important approaches that are advancing simple, rapid, in vivo expression and having an impact in animal models of infectious diseases and cancer, among others.


id: cord-010991-fp8hljbq
author: Rather, Shabeer Ahmad
date: 2020-01-03
txt: ./txt/cord-010991-fp8hljbq.txt
cache: ./cache/cord-010991-fp8hljbq.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7223241/
doi: 10.1007/s00253-019-10327-x
summary:
  For vaccine development, attention was paid on the purified antigens involved in the pathogenesis of dental caries for the development of potentially safer vaccines, which may reduce the viability of bacteria in the saliva, impairing the surface adhesion and inhibiting the metabolically active enzymes involved in caries formation (Chen and Wang 2010) . mutans have shown encouraging results related to dental caries protection, but were limited by the cross-reactive epitopes against human heart and skeleton muscle tissues as detected by indirect immunofluorescence and crossed immunoelectrophoresis (Kt et al. In the present study, we have tried to evaluate the effect of anti-dextransucrase antibodies on caries formation by using purified dextransucrase as the antigen from S. Protein samples of the liver, heart, spleen, kidney of mice, rat and liver, kidney of rabbit were analysed by western blot analysis to evaluate the cross reactivity of purified antibody with mammalian tissues Fig. 5a .

title:
  Antibodies generated against dextransucrase exhibit potential anticariostatic properties in Streptococcus mutans

abstract:
  Streptococcus mutans is a common principal causative agent of dental caries. In this communication, we describe that the antibodies raised against purified dextransucrase effectively inhibited the growth of S. mutans. The purified enzyme showed 58-fold enrichment, 17.5% yield and a specific activity of 3.96 units/mg protein. Purified IgG fraction of the antibody showed significant affinity with the antigenic protein. Immunotritation of the enzyme with dextransucrase antibody showed a gradual increase in inhibition of dextransucrase activity. The growth of S. mutans was also inhibited by 85% in the presence of 28 μg of IgG fraction of the antibody. Antibodies also impaired glucosyltransferase activity (72.8%) and biofilm formation by 92.6% in S. mutans. Western blot analysis revealed no cross reactivity with the various tissues of mice, rat, rabbit and humans. Dot blot analysis showed little reactivity with Lactobacillus acidophilus and Staphylococcus aureus and there was no reactivity with other bacterial strains like Enterococcus faecalis, Escherichia coli and Salmonella typhimurium. These findings suggest that antibody raised against dextransucrase exhibit inhibitory effects on the growth of S. mutans and biofilm formation with no reactivity with various mammalian tissues, thus it could be an effective anticariogenic agent.


id: cord-015683-a9a82of4
title: Molecular Diagnostics
author: Gupta, Varsha
date: 2016-10-23
txt: ./txt/cord-015683-a9a82of4.txt
cache: ./cache/cord-015683-a9a82of4.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7115026/
doi: 10.1007/978-981-10-0875-7_9
summary:
  Molecular diagnostics such as Western blot , ELISA , PCR , DNA, and protein microarrays are 7 revolutionizing the clinical practice of infectious diseases. Molecular diagnostics such as Western blot , ELISA , PCR , DNA, and protein microarrays are 7 revolutionizing the clinical practice of infectious diseases. Binding of another antigen-specifi c antibody linked with enzyme results in color formation upon addition of the substrate 9.2 Diagnosis of Bacterial, Viral, and Parasitic Diseases peptide may react in some assays but not in others as some regions of a peptide may be more immunogenic than others. Because of the specifi city, homogeneity, and unlimited availability of the MAbs, vast amount of work has been carried out on the production/development The immuno-diagnoses of protozoan and parasitic diseases have signifi cantly been improved by MAb technology because the tests involving MAb as diagnostic reagents overcome the limitations of polyclonal antibodies. The sensitivity and specifi city of a PCR assay is dependent on target genes, primer sequences, PCR techniques, DNA extraction procedures, and PCR product detection methods.

abstract:
  Effective and early management of diseases requires record of the history, behavioral parameters, and travel information. These are helpful for the diagnosis, prevention, and control of the disease. There have been several advancements in the methods for diagnosing infectious diseases. The wide spectrum of tests such as biochemical evaluation, microbiological tools, immunological and molecular biology techniques, etc., is available. Each type of diagnostic technique is strong and reliable in its own sense but poses certain limitations. These limitations may be complemented by using a combination of tests. Older techniques such as microscopy and culturing of organisms from clinical specimens are error-free but are very labor intensive and extremely time consuming. There is a need to develop rapid and sensitive tests that can be used in both high- and low-resource settings. Molecular diagnostics such as Western blot, ELISA, PCR, DNA, and protein microarrays are revolutionizing the clinical practice of infectious diseases. Their effects are significant in acute-care settings where timely and accurate diagnostic tools are critical for patient treatment decisions and outcomes.


id: cord-015742-nt44jcjm
title: Antigenicity of structural components from porcine transmissible gastroenteritis virus
author: Garwes, D.J.
date: 2002-11-13
txt: ./txt/cord-015742-nt44jcjm.txt
cache: ./cache/cord-015742-nt44jcjm.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7117557/
doi: 10.1016/0378-1135(79)90034-8
summary:
  Incubation of 3H-uridine TGEV with sera from sows inoculated with viral antigen resulted in the formation of immune complexes that were retained by membrane filters (Fig. 2) . Sera from sows inoculated with whole virus, SP antigen or SVP antigen preparations produced virus complexes that were retained most efficient Samples of 3H-uridine labelled TGEV containing 4000 ct/min were incubated for 2 h at 37°C in dilutions of test sera followed by incubation with rabbit anti-porcine IgG serum. Analysis of the immunoglobulin classes responsible for neutralising activity after inoculation of sows by the intramammary route showed that IgG was the predominant antibody species in both serum and colostrum, consistent with previous findings with inactivated TGEV Lucas et al., 1974) but differing from the stimulation of IgA to ferritin reported by Bourne et al. 9, which received SP antigen, produced neutralising antibody of the IgA class in the colostrum and was the only animal capable of protecting her piglets against challenge with live virus.

abstract:
  Pregnant sows were inoculated with inactivated transmissible gastroenteritis virus and with preparations of virus surface projections and subviral particles derived by detergent treatment of the virus. Neutralising antibody was demonstrated in serum and colostrum from animals that received whole virus or preparations of surface projections whereas subviral particles failed to stimulate neutralising antibody formation. Similar results were obtained with serum from rabbits inoculated with whole virus and structural components. All three preparations stimulated the formation of agglutinating antibodies, as demonstrated by sedimentation analysis and filtration studies with radiolabelled virus. The immunoglobulin classes responsible for neutralising antibody activity in sows inoculated by the intramammary route were examined. In each case where the immunoglobulin class was determined, IgG was found. One sow that received surface projections also had IgA with neutralising activity in her colostrum. In contrast, infection of sows with live whole virus resulted in neutralising antibody of the IgG, IgM and IgA classes.


id: cord-016960-xhzvp35g
author: Berencsi, György
date: 2012-03-08
txt: ./txt/cord-016960-xhzvp35g.txt
cache: ./cache/cord-016960-xhzvp35g.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7121401/
doi: 10.1007/978-94-007-4216-1_9
summary:
  The importance of maternal anti-idiotypic antibodies are believed to prime the fetal immune system with epitopes of etiologic agents infected the mother during her whole life before pregnancy and delivery. Neonatal lupus is a model of passively acquired autoimmunity in which a mother-, who may have systemic lupus erythematosus (SLE) or Sj€ ogren''s syndrome (SS) or may be entirely asymptomatic-synthesizes antibodies to SSA/Ro and/or SSB/ La ribonucleoproteins that enter the fetal circulation via trophoblast FcRn receptors and presumably cause tissue injury (Lee 1990 ) as mentioned above. Teplizumab (CD3-specific, hOKT3g1-Ala-Ala), a humanized Fc mutated anti-CD3 monoclonal antibody induced tolerance, on the progression of type 1 diabetes in patients with recent-onset disease even 2 years after the first diagnosis (Herold et al. Clinical and immune responses in resected colon cancer patients treated with anti-idiotype monoclonal antibody vaccine that mimics the carcinoembryonic antigen Clinical use of anti-CD25 antibody daclizumab to enhance immune responses to tumor antigen vaccination by targeting regulatory T cells

title:
  Fetal and Neonatal Illnesses Caused or Influenced by Maternal Transplacental IgG and/or Therapeutic Antibodies Applied During Pregnancy

abstract:
  The human fetus is protected by the mother’s antibodies. At the end of the pregnancy, the concentration of maternal antibodies is higher in the cord blood, than in the maternal circulation. Simultaneously, the immune system of the fetus begins to work and from the second trimester, fetal IgM is produced by the fetal immune system specific to microorganisms and antigens passing the maternal-fetal barrier. The same time the fetal immune system has to cope and develop tolerance and T(REG) cells to the maternal microchimeric cells, latent virus-carrier maternal cells and microorganisms transported through the maternal-fetal barrier. The maternal phenotypic inheritance may hide risks for the newborn, too. Antibody mediated enhancement results in dengue shock syndrome in the first 8 month of age of the baby. A series of pathologic maternal antibodies may elicit neonatal illnesses upon birth usually recovering during the first months of the life of the offspring. Certain antibodies, however, may impair the fetal or neonatal tissues or organs resulting prolonged recovery or initiating prolonged pathological processes of the children. The importance of maternal anti-idiotypic antibodies are believed to prime the fetal immune system with epitopes of etiologic agents infected the mother during her whole life before pregnancy and delivery. The chemotherapeutical and biological substances used for the therapy of the mother will be transcytosed into the fetal body during the last two trimesters of pregnancy. The long series of the therapeutic monoclonal antibodies and conjugates has not been tested systematically yet. The available data are summarised in this chapter. The innate immunity plays an important role in fetal defence. The concentration of interferon is relative high in the placenta. This is probably one reason, why the therapeutic interferon treatment of the mother does not impair the fetal development.


id: cord-016966-b23o5roz
title: Immune response in human pathology: infections caused by bacteria, viruses, fungi, and parasites
author: Verhoef, Jan
date: 2005
txt: ./txt/cord-016966-b23o5roz.txt
cache: ./cache/cord-016966-b23o5roz.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7121408/
doi: 10.1007/3-7643-7408-x_7
summary:
  Effective treatment, however, was not possible at that time; prevention and spread of infectious diseases depended solely on proper hygienic means.At the beginning of the 20th century, passive and active vaccination procedures were developed against a number of these pathogenic micro-organisms in order to prevent the diseases in question (rabies, diphtheria, tetanus, etc.) and due to the discovery of antimicrobial chemicals (Ehrlich) and antibiotics (Fleming), the threat of infectious diseases seemed to be minimized. CYTOKINES, such as IL-2 (INTERLEUKIN-2), GM-CSF (granulocyte-macrophage colony-stimulating factor), and TNF-α (TUMOR NECROSIS FACTOR α), stimulate non-specifically the proliferation, maturation, and Immune response in human pathology: infections caused by bacteria, viruses, fungi, and parasites Jan Verhoef and Harm Snippe A7 function of the cells involved in defence (see Chapter A.4).

abstract:
  Despite the introduction of effective health measurements, vaccination and antimicrobial therapy infectious diseases continue to threaten human life. The reasons are numerous and diverse: antibiotic resistance, hospital-invading pathogens, new emerging infectious diseases, bioterrorism, biological warfare. This chapter is an introduction to several aspects of infectious diseases viewed from the host as well as from the pathogen (bacterium, virus and parasite). Furthermore the basic principles of INNATE and ADAPTIVE IMMUNE RESPONSES, especially in debilitated patients, are described. Detailed information is given on the pathogenesis of septic shock, AIDS and vaccination strategies.


id: cord-017070-05vlz5dn
title: Human Monoclonal Antibodies Against HIV and Emerging Viruses
author: Dimitrov, Dimiter S.
date: 2008
txt: ./txt/cord-017070-05vlz5dn.txt
cache: ./cache/cord-017070-05vlz5dn.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7121542/
doi: 10.1007/978-1-59745-569-5_34
abstract: nan
summary:
  These antibodies also protected uninfected animals from SARS-CoV infection, e.g., passive transfer of immune serum to naive mice prevented virus replication in the lower respiratory tract following intranasal challenge (61) . Recently, an improved method for Epstein-Barr virus transformation of human B cells has been developed based on CpG oligonucleotide (CpG 2006) that increases the B cell immortalization efficiency from 1-2% to 30-100%, and used for selection of hmAbs specific for SARS-CoV proteins (68) . We have recently identified a novel cross-reactive potent SARS-CoV-neutralizing hmAb, m396, by using a fragment containing residues 317 through 518 as a selecting antigen for panning of a large human antibody library constructed from the B lymphocytes of healthy volunteers (75) . These antibodies specific for SARS-CoV, HeV, and NiV have potential for further development into a clinically useful product for prophylaxis and perhaps treatment of the diseases caused by these infections. Potent neutralization of severe acute respiratory syndrome (SARS) coronavirus by a human mAb to S1 protein that blocks receptor association


id: cord-018404-jdu4h00e
author: DuBourdieu, Dan
date: 2019-03-11
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7123268/
doi: 10.1007/978-3-030-04624-8_18
title:
  Colostrum Antibodies, Egg Antibodies and Monoclonal Antibodies Providing Passive Immunity for Animals

abstract:
  Passive immunity can be provided to animals by several sources of antibodies including from colostrum, avian eggs, and monoclonal sources. These antibodies have been shown protect production and companion animals from a number of pathogens. This chapter reviews the immune system for the principles of immune response to antigens and the synthesis of immunoglobulins of the five classes of antibodies in the body. Colostrum antibodies are described for passive immunity protection in animals such as calves. Chicken egg antibodies are another source of antibodies for passive immunity. Therapeutic monoclonal antibodies are also used to provide passive immunity in the veterinary field.


id: cord-018811-zhwr3h07
author: Oxford, John
date: 2010-06-18
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7123788/
doi: 10.1007/978-3-0346-0279-2_6
title:
  Influenza Vaccines Have a Short but Illustrious History of Dedicated Science Enabling the Rapid Global Production of A/Swine (H1N1) Vaccine in the Current Pandemic

abstract:
  Vaccines for the swine flu pandemic of 2009 have been produced in an exquisitely short time frame. This speed of production comes because of 50 years of hard work by virologists worldwide in pharma groups, research laboratories, and government licensing units. The present chapter presents the background framework of influenza vaccine production and its evolution over 50 years. Isolation of the causative virus of influenza in 1933, followed by the discovery of embryonated hen eggs as a substrate, quickly led to the formulation of vaccines. Virus-containing allantoic fluid was inactivated with formalin. The phenomenon of antigenic drift of the virus HA was soon recognized and as WHO began to coordinate the world influenza surveillance, it became easier for manufacturers to select an up-to-date virus. Influenza vaccines remain unique in that the virus strain composition is reviewed yearly, but modern attempts are being made to free manufacturers from this yolk by investigating internal virus proteins including M2e and NP as “universal” vaccines covering all virus subtypes. Recent technical innovations have been the use of Vero and MDCK cells as the virus cell substrate, the testing of two new adjuvants, and the exploration of new presentations to the nose or epidermal layers as DNA or antigen mixtures. The international investment into public health measures for a global human outbreak of avian H5N1 influenza together with a focus of swine influenza H1N1 is leading to enhanced production of conventional vaccine and to a new research searchlight on T-cell epitope vaccines, viral live-attenuated carriers of influenza proteins, and even more innovative substrates to cultivate virus, including plant cells.


id: cord-018840-ts2g1ux7
title: Role of Immunoglobulin Therapy to Prevent and Treat Infections
author: Katragkou, Aspasia
date: 2018-06-19
txt: ./txt/cord-018840-ts2g1ux7.txt
cache: ./cache/cord-018840-ts2g1ux7.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7123824/
doi: 10.1007/978-3-319-77674-3_17
summary:
  While the main clinical applications of immunoglobulin therapy concern their use as replacement for patients with primary immunodeficiencies, or as treatment for autoimmune and inflammatory disorders, their role in infectious disease is limited largely to viral and toxin neutralization and replacement therapy in patients with immunoglobulin deficiencies. The first clinical trial, which evaluated the effect of IgMA-enriched immunoglobulin preparation (7.8 g IgM, 7.8 g IgA, and 49.4 g IgG), which have shown to contain superior antibody content against bacterial lipopolysaccharides, in an appreciable number of neutropenic patients with hematologic malignancies and sepsis or septic shock, showed that immunoglobulins had no beneficial effects [51] . A controlled trial of long-term administration of intravenous immunoglobulin to prevent late infection and chronic graft-vs.-host disease after marrow transplantation: clinical outcome and effect on subsequent immune recovery

abstract:
  Immunoglobulins have been used widely in medicine for a variety of diseases including infectious diseases. While the main clinical applications of immunoglobulin therapy concern their use as replacement for patients with primary immunodeficiencies, or as treatment for autoimmune and inflammatory disorders, their role in infectious disease is limited largely to viral and toxin neutralization and replacement therapy in patients with immunoglobulin deficiencies. Many aspects of the therapeutic regimen of immunoglobulins even in the established indications remain open. Recently, due to the worldwide surge of immunosuppression caused by AIDS, organ transplantation, cancer, and autoimmune therapies, as well as the emergence of multidrug-resistant bacteria, there has been renewed interest in the use of antibody preparation to prevent infections in high-risk groups. Knowing the limitations of the current anti-infective armamentarium, approaches that target the host through manipulations to augment the host immune response provide a helpful aid to conventional treatment options. A substantial body of evidence has demonstrated that strategies aiming to support or stimulate immune response could be feasible approaches that would benefit immunocompromised patients. In the present chapter, we present contemporary indications of immunoglobulin administration for therapy and prophylaxis of infections in the immunocompromised population.


id: cord-021402-wq770ik9
title: New Diagnostic Tools for Infectious Disease
author: Relford, Roberta L.
date: 2009-05-15
txt: ./txt/cord-021402-wq770ik9.txt
cache: ./cache/cord-021402-wq770ik9.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7149580/
doi: 10.1016/b0-72-160423-4/50009-3
abstract: nan
summary:
  The most common laboratory methodologies used to identify an infectious agent include visualization of the organism via cytology/biopsy, isolation of the agent in microbiological culture, immunodiagnostics/serology, and nucleic acid technology. Fluorescent antibody and immunoblot assays are performed in commercial laboratories, whereas numerous patient-side rapid ELISA and latex agglutination kits are available for antigen detection. Until the introduction of nucleic acid amplification by the PCR, detection of an organism''s DNA or RNA often was impossible because of the small amount of antigen present in a sample. In the ELISA and IFA antibody assays, a specific antigen from the infectious agent in question is fixed to a solid surface (microtiter plate or glass slide, respectively) and the patient''s serum is added. The SVN assay evaluates the ability of antibodies in a patient''s serum to prevent the infection of culture cells or embryonated eggs with a known specific virus.


id: cord-021770-zn7na974
title: Passive Immunization
author: Slifka, Mark K.
date: 2017-07-17
txt: ./txt/cord-021770-zn7na974.txt
cache: ./cache/cord-021770-zn7na974.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7151993/
doi: 10.1016/b978-0-323-35761-6.00008-0
abstract: nan
summary:
  [26] [27] [28] [29] Recent studies verify these earlier results, demonstrating a 90% to 91% vaccine efficacy against whooping cough among infants younger than 2 months of nonlymphoid tissues and to penetrate mucosal sites of infection is likely to explain why it is often considered the best immunoglobulin isotype for routine passive immunization and has shown clinical benefit ranging from reduced clinical symptoms to nearly complete protection from lethal infection in a number of infectious disease models (Table 8 .3). 118 With the recent development of polyclonal and monoclonal antibodies that show protective efficacy against tularemia in animal models, [119] [120] [121] it may be possible to incorporate both passive immunotherapy and antibiotic treatment into clinical practice not only for tularemia, but for other bacterial diseases, especially in cases in which antibiotic resistance is becoming more widespread.


id: cord-022310-yc6xtw0s
title: Microbiology and Infectious Disease
author: Lappin, Michael R.
date: 2011-12-15
txt: ./txt/cord-022310-yc6xtw0s.txt
cache: ./cache/cord-022310-yc6xtw0s.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7155555/
doi: 10.1016/b978-1-4377-0657-4.00015-6
abstract: nan
summary:
  47 Because of these findings, it is currently recommended to combine serologic test results with those of blood culture or PCR assay results when evaluating clinically ill cats for bartonellosis. Because serologic test results do not accurately correlate with presence of bacteremia and individual culture or PCR assay results can be falsely negative, there is no indication for testing healthy cats for Bartonella spp. T. gondii-specific IgM is detectable in serum by ELISA in approximately 80% of subclinically ill cats 2 to 4 weeks after experimental induction of toxoplasmosis; these titers generally are negative less than 16 weeks after infection. The author, however, has demonstrated IgG antibody titers greater than 1 : 16,384 in subclinically ill cats 5 years after experimental induction In chronic disease or asymptomatic carriers, demonstration of organisms is unreliable, and a tentative diagnosis is based on clinical signs and a positive titer. gondii-specific antibodies can also be detected in the serum, CSF, and aqueous humor of healthy, infected animals, one cannot assay results in clinically ill dogs, E.


id: cord-023053-j061ywrl
title: Cats, coronaviruses and coronavirus antibody tests
author: BARLOUGH, J. E.
date: 2008-04-10
txt: ./txt/cord-023053-j061ywrl.txt
cache: ./cache/cord-023053-j061ywrl.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7166406/
doi: 10.1111/j.1748-5827.1985.tb02210.x
summary:
  In domestic and exotic cats, FIPV is the aetiologic agent of a lethal disease-feline infectious peritonitis (FIP)-characterized by fibrinous serositis, vasculitis, and formation of disseminated pyogranulomas (Wolfe & Griesemer. Laboratory test procedures for detection of coronavirus antibody in feline sera include biological assays such as virus neutralization (VN); non-biological, immunochemical techniques such as indirect immunofluorescence assay (IFA), enzyme-linked immunosorbent assay (ELISA), and kinetics-based ELISA (KELA); and other methods such as agar gel immunodiffusion and passive haemagglutination , though the availability of such tests varies worldwide. The serodiagnostic potential of these assays (i.e., their ability to identify cats with active FIP and/or potential virus carriers/excretors) is thus limited not only by the widespread distribution of serum coronavirus antibody in the feline population, but also by the possibility that non-FIPV coronaviruses may be responsible for some of the seroconversions that they detect.

abstract:
  Feline infectious peritonitis and other coronavirus infections of cats are briefly reviewed. Interpretation and applications of feline coronavirus antibody tests are described, and general recommendations are provided for practitioners. Some of the major unresolved questions regarding coronavirus infections of cats are delineated.


id: cord-023346-8sqbqjm1
title: MONDAY: POSTERS
author: nan
date: 2005-06-08
txt: ./txt/cord-023346-8sqbqjm1.txt
cache: ./cache/cord-023346-8sqbqjm1.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7169255/
doi: 10.1111/j.1423-0410.2005.00652.x
abstract: nan
summary:
  • enhancement of automation/computerisation; • process control to provide an ''error-free pathway''; • (national) surveillance and trend analysis of results, preferably based on national working standards; • significantly increased sensitivity, especially from development of antigen/antibody ''combi'' assays (e.g. for HIV, and recently, for HCV); • awareness of HBsAg vaccine-escape mutants and design of assays to cope with this; • extension of range of agents and markers tested for (varies in different countries); • increasing range of assays available for testing donors with a relevant history of exposure to malaria or Chagas'' disease infection (for retrieval of otherwise wasted blood); • European Union''s in vitro diagnostics directive: this has caused some problems and reduced flexibility.


id: cord-023731-jqgervt7
title: Laboratory Diagnosis of Viral Diseases
author: FENNER, FRANK
date: 2014-06-27
txt: ./txt/cord-023731-jqgervt7.txt
cache: ./cache/cord-023731-jqgervt7.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7173550/
doi: 10.1016/b978-0-12-253055-5.50017-7
summary:
  Having allocated it to a particular family (e.g., Adenoviridae), one can then go on to determine the species or serotype (e.g., canine Immunodiffusion Antibody neutralizes infectivity of virion; inhibits cytopathology, reduces plaques, or protects animals Antibody inhibits viral hemagglutination Antigen-antibody complex binds complement, which is thereafter unavailable for the lysis of hemolysissensitized sheep red blood cells Antibody-aggregated virions are visible by electron microscopy Antibody labeled with fluorochrome binds to intracellular antigen; fluoresces by UV microscopy Peroxidase-labeled antibody binds to intracellular antigen; colored precipitate forms on adding substrate Enzyme-labeled antibody (or antigen) binds to antigen (or antibody); substrate changes color Radiolabeled antibody (or antigen) binds to antigen (or antibody), e.g., attached to solid phase Antibodies and soluble antigens produce visible lines of precipitate in a gel adenovirus 1) by more discriminating serological procedures.

abstract:
  Tests for the specific diagnosis of a viral infection in an animal are of two general types: (1) those that demonstrate the presence of the virus and (2) those that demonstrate the presence of specific viral antibody. The provision, by a single laboratory, of a comprehensive service for the diagnosis of viral infections of domestic animals is a formidable undertaking. There are about 200 individual viral species in some 20 different viral families that infect the eight major domestic animal species. If antigenic types within an individual viral species are considered and the number of animal species is broadened to include turkey, duck, and zoo and laboratory animals, then the number of individual viruses exceeds 1000. It is, therefore, not surprising that few single laboratories could have available the necessary specific reagents, skills, and experience for the diagnosis of such a large number of infections.


id: cord-030999-27wennun
title: Adaptive immunity to SARS-CoV-2
author: Altmann, Daniel M
date: 2020-07-09
txt: ./txt/cord-030999-27wennun.txt
cache: ./cache/cord-030999-27wennun.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7454881/
doi: 10.1093/oxfimm/iqaa003
summary:
  The majority of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 exposed individuals mount an antibody response within around 2-weeks and spike antigen-binding responses correlate well with functional virus neutralization. Studies of T-cell immunity following acute infection show CD4 and CD8 responses to epitopes across diverse viral antigens, possible cross-reactivity with epitopes from the common cold human coronaviruses and large-scale activation. Since many key questions about durability of the antibody response and about correlates of protection have been hard to address in this short timeframe, there has been value in recourse to the coronavirus immunology literature, especially in relation to SARS and MERS [16] [17] [18] [19] . Experience to date with SARS-CoV-2 suggests that this may not prove to be an infection that throws up insurmountable confounders to vaccine design-approaches that can safely and durably elicit neutralizing antibody look likely to work. Antibody responses against SARS coronavirus are correlated with disease outcome of infected individuals

abstract:
  The majority of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 exposed individuals mount an antibody response within around 2-weeks and spike antigen-binding responses correlate well with functional virus neutralization. A minority makes little detectable antibody, generally those with either very mild/asymptomatic disease or those with severe/lethal infection. However, in general, antibody titre correlates with viral load and duration of exposure. There is evidence for cross-reactivity with the other human coronaviruses, though the functional impact of this is as yet unclear. Therapeutic use of neutralizing monoclonal antibodies offers potential for clinical use. While there is evidence for neutralizing antibody as a correlate of protection, some cases indicate the potential for full recovery in the absence of antibody. Studies of T-cell immunity following acute infection show CD4 and CD8 responses to epitopes across diverse viral antigens, possible cross-reactivity with epitopes from the common cold human coronaviruses and large-scale activation. However, in severe cases, there is evidence for T-cell lymphopaenia as well as expression of exhaustion markers. Analysis of serum biomarkers of disease severity implicates a hyperinflammatory contribution to pathogenesis, though this has not been mechanistically delineated beyond a likely role of raised IL-6, considered a therapeutic target. Despite rapid progress, there remain pressing unknowns. It seems likely that immune memory to SARS-CoV-2 may be relatively short lived, but this will need longitudinal investigation. Also, this is a disease of highly variable presentation and time course, with some progressing to protracted, chronic symptoms, which are not understood. The contribution of immunopathological mechanisms to tissue damage, whether in the lung, kidney, heart or blood vessels, is unclear. The immunology underlying the differential susceptibility between the very young and the very old is unresolved, a question with ramifications for vaccine roll-out. The greatest challenge relates to rapid generation, testing and manufacture of vaccines that are immunogenic, protective (at least from symptomatic disease) and safe—a challenge that looks achievable.


id: cord-031060-0o9agjiq
author: Yuan, Tom Z
date: 2020-08-01
txt: ./txt/cord-031060-0o9agjiq.txt
cache: ./cache/cord-031060-0o9agjiq.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7454256/
doi: 10.1093/abt/tbaa016
summary:
  Incorporating epitope binning on hundreds of antibodies during early stage antibody characterization ensures access to a library''s full epitope coverage, aids in the identification of high quality reagents within the library that recapitulate this diversity for use in other studies, and ultimately enables the rational development of therapeutic cocktails that take advantage of multiple mechanisms of action such as cooperative synergistic effects to enhance neutralization function and minimize the risk of mutagenic escape. Despite ligand attrition and the stringent requirement for premixed antibodies to achieve antigen saturation, which reduced our heat map to 52 analytes x 233 ligands, we were able in this non-optimized ''first pass'' binning to assign 234 antibodies to one of seven epitope communities without the use of benchmark antibodies (Supplemental Table S1 ).

title:
  Rapid exploration of the epitope coverage produced by an Ebola survivor to guide the discovery of therapeutic antibody cocktails

abstract:
  BACKGROUND: Development of successful neutralizing antibodies is dependent upon broad epitope coverage to increase the likelihood of achieving therapeutic function. Recent advances in synthetic biology have allowed us to conduct an epitope binning study on a large panel of antibodies identified to bind to Ebola virus glycoprotein with only published sequences. METHODS AND RESULTS: A rapid, first-pass epitope binning experiment revealed seven distinct epitope families that overlapped with known structural epitopes from the literature. A focused set of antibodies was selected from representative clones per bin to guide a second-pass binning that revealed previously unassigned epitopes, confirmed epitopes known to be associated with neutralizing antibodies, and demonstrated asymmetric blocking of EBOV GP from allosteric effectors reported from literature. CONCLUSIONS: Critically, this workflow allows us to probe the epitope landscape of EBOV GP without any prior structural knowledge of the antigen or structural benchmark clones. Incorporating epitope binning on hundreds of antibodies during early stage antibody characterization ensures access to a library’s full epitope coverage, aids in the identification of high quality reagents within the library that recapitulate this diversity for use in other studies, and ultimately enables the rational development of therapeutic cocktails that take advantage of multiple mechanisms of action such as cooperative synergistic effects to enhance neutralization function and minimize the risk of mutagenic escape. The use of high-throughput epitope binning during new outbreaks such as the current COVID-19 pandemic is particularly useful in accelerating timelines due to the large amount of information gained in a single experiment.


id: cord-032598-i0jm3p1s
title: Direct imaging of antigen–antibody binding by atomic force microscopy
author: Hu, Jing
date: 2020-09-24
txt: ./txt/cord-032598-i0jm3p1s.txt
cache: ./cache/cord-032598-i0jm3p1s.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7511526/
doi: 10.1007/s13204-020-01558-w
summary:
  In this study, the morphology of biotinylated antibody-specific Immunoglobulin E (IgE) immune complexes has been successfully imaged by atomic force microscopy (AFM) in the tapping-mode. The AFM images indicated that the individual immune complex was composed of an IgE and a biotinylated antibody. To the best of our knowledge, the biotinylated antibody-specific IgE immune complexes imaged by AFM have never been reported. Meanwhile, Fig. 6d , h and l would represent the biotinylated antibody-specific IgE immune complex adsorbed on the mica surface by the IgE fragment and the two Fab fragments of biotinylated antibody. In this paper, the morphology and length of IgE, biotinylated antibodies and biotinylated antibody-specific IgE immune complexes were analyzed by AFM, respectively. The results of AFM imaging demonstrated that the immune complexes exhibited various morphologies, and we were able to identify the IgE and biotinylated antibody based on the protein morphology in most cases.

abstract:
  Direct observation of antigen–antibody binding at the nanoscale has always been a considerable challenging problem, and researchers have made tremendous efforts on it. In this study, the morphology of biotinylated antibody-specific Immunoglobulin E (IgE) immune complexes has been successfully imaged by atomic force microscopy (AFM) in the tapping-mode. The AFM images indicated that the individual immune complex was composed of an IgE and a biotinylated antibody. Excitingly, it is the first time that we have actually seen the IgE binding to biotinylated antibody. Alternatively, information on the length of IgE, biotinylated antibodies and biotinylated antibody-specific IgE immune complexes were also obtained, respectively. These results indicate the versatility of AFM technology in the identification of antigen–antibody binding. This work not only lays the basis for the direct imaging of the biotinylated antibody-IgE by AFM, but also offers valuable information for studying the targeted therapy and vaccine development in the future. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s13204-020-01558-w) contains supplementary material, which is available to authorized users.


id: cord-048239-oluq7v0h
title: Development of a humanized monoclonal antibody with therapeutic potential against West Nile virus
author: Oliphant, Theodore
date: 2005-04-24
txt: ./txt/cord-048239-oluq7v0h.txt
cache: ./cache/cord-048239-oluq7v0h.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1458527/
doi: 10.1038/nm1240
summary:
  Using random mutagenesis and yeast surface display, we defined individual contact residues of 14 newly generated monoclonal antibodies against domain III of the WNV E protein. Development of a humanized monoclonal antibody with therapeutic potential against West Nile virus E protein by nickel-affinity chromatography (data not shown). 24 ), yet was virus specific, as it neither recognized nor neutralized other flaviviruses including distantly related dengue and yellow fever viruses (data not shown) and closely related Japanese and St. Louis encephalitis viruses (Supplementary Table 2 Figure 1 Mapping of monoclonal antibodies to DIII with yeast. None of the mutations identified by loss-of-binding sorts for E2 or E22 had any effect on two other non-neutralizing monoclonal Individual WNV-specific monoclonal antibodies (25 µg/ml) were mixed with yeast that displayed wild-type or mutant DIII on their surface. To determine whether human antibodies specific for WNV recognize the neutralizing epitope on DIII during infection, plasma was obtained from WNV-positive individuals.

abstract:
  Neutralization of West Nile virus (WNV) in vivo correlates with the development of an antibody response against the viral envelope (E) protein. Using random mutagenesis and yeast surface display, we defined individual contact residues of 14 newly generated monoclonal antibodies against domain III of the WNV E protein. Monoclonal antibodies that strongly neutralized WNV localized to a surface patch on the lateral face of domain III. Convalescent antibodies from individuals who had recovered from WNV infection also detected this epitope. One monoclonal antibody, E16, neutralized 10 different strains in vitro, and showed therapeutic efficacy in mice, even when administered as a single dose 5 d after infection. A humanized version of E16 was generated that retained antigen specificity, avidity and neutralizing activity. In postexposure therapeutic trials in mice, a single dose of humanized E16 protected mice against WNV-induced mortality, and may therefore be a viable treatment option against WNV infection in humans. SUPPLEMENTARY INFORMATION: The online version of this article (doi:10.1038/nm1240) contains supplementary material, which is available to authorized users.


id: cord-048360-n9sih438
title: Rapid Identification of Malaria Vaccine Candidates Based on α-Helical Coiled Coil Protein Motif
author: Villard, Viviane
date: 2007-07-25
txt: ./txt/cord-048360-n9sih438.txt
cache: ./cache/cord-048360-n9sih438.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1920550/
doi: 10.1371/journal.pone.0000645
summary:
  To identify malaria antigens for vaccine development, we selected α-helical coiled coil domains of proteins predicted to be present in the parasite erythrocytic stage. Here, we focus on the Pf parasite erythrocytic stage, a target of protective antibodies and describe a straightforward, rapid procedure based on bioinformatic analysis of a-helical coiled-coil motifs and peptide synthesis. With regard to the structural features and cellular location prediction of the proteins corresponding to the peptides selected for ADCI assays ( Table 1) , 15 of the proteins contain a pentapeptide conforming to the PEXEL consensus [19, 20; 21, 22] , but that none of these have a position within the amino acid sequence that conforms to the location of known active PEXEL motifs (see Materials and Methods and membrane segments, and none of them has a GPI anchor. In conclusion, an approach combining a genome-wide search by bioinformatics of a-helical coiled coil protein motifs and chemical synthesis can lead to the rapid identification and development of new malaria vaccine candidates.

abstract:
  To identify malaria antigens for vaccine development, we selected α-helical coiled coil domains of proteins predicted to be present in the parasite erythrocytic stage. The corresponding synthetic peptides are expected to mimic structurally “native” epitopes. Indeed the 95 chemically synthesized peptides were all specifically recognized by human immune sera, though at various prevalence. Peptide specific antibodies were obtained both by affinity-purification from malaria immune sera and by immunization of mice. These antibodies did not show significant cross reactions, i.e., they were specific for the original peptide, reacted with native parasite proteins in infected erythrocytes and several were active in inhibiting in vitro parasite growth. Circular dichroism studies indicated that the selected peptides assumed partial or high α-helical content. Thus, we demonstrate that the bioinformatics/chemical synthesis approach described here can lead to the rapid identification of molecules which target biologically active antibodies, thus identifying suitable vaccine candidates. This strategy can be, in principle, extended to vaccine discovery in a wide range of other pathogens.


id: cord-102704-wfuzk2dp
author: Meza, Diana K.
date: 2020-04-30
txt: ./txt/cord-102704-wfuzk2dp.txt
cache: ./cache/cord-102704-wfuzk2dp.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1101/2020.04.24.060095
doi: 10.1101/2020.04.24.060095
summary:
  Despite small conflicts, titer predictions were correlated across tests repeated on different dates both for dog samples (r = 0.93), and for a second dataset of sera from wild common vampire bats (r = 0.72, N = 41), indicating repeatability. The pmRFFIT enables high-throughput detection of rabies virus neutralizing antibodies in low-biocontainment settings and is suited to studies in wild or captive animals where large serum volumes cannot be obtained. The binomial and log-normal models fit to 193 this data subset included only the fixed effect of the virus-infected N2A cell counts, but the random 194 effects were identical to those explained above (i.e. test date and field). A final distinction is that 316 instead of scoring microscope field or wells as virus positive or negative, the pmRFFIT predicts 317 serological status and RVNA titer from infected cell counts in a single serum dilution using statistical 318

title:
  Predicting the presence and titer of rabies virus neutralizing antibodies from low-volume serum samples in low-containment facilities

abstract:
  Serology is a core component of the surveillance and management of viral zoonoses. Virus neutralization tests are a gold standard serological diagnostic, but requirements for large volumes of serum and high biosafety containment can limit widespread use. Here, focusing on Rabies lyssavirus, a globally important zoonosis, we developed a pseudotype micro-neutralization rapid fluorescent focus inhibition test (pmRFFIT) that overcomes these limitations. Specifically, we adapted an existing micro-neutralization test to use a green fluorescent protein–tagged murine leukemia virus pseudotype in lieu of pathogenic rabies virus, reducing the need for specialized reagents for antigen detection and enabling use in low-containment laboratories. We further used statistical analysis to generate rapid, quantitative predictions of the probability and titer of rabies virus neutralizing antibodies from microscopic imaging of neutralization outcomes. Using 47 serum samples from domestic dogs with neutralizing antibody titers estimated using the fluorescent antibody virus neutralization test (FAVN), pmRFFIT showed moderate sensitivity (78.79%) and high specificity (84.62%). Despite small conflicts, titer predictions were correlated across tests repeated on different dates both for dog samples (r = 0.93), and for a second dataset of sera from wild common vampire bats (r = 0.72, N = 41), indicating repeatability. Our test uses a starting volume of 3.5 μL of serum, estimates titers from a single dilution of serum rather than requiring multiple dilutions and end point titration, and may be adapted to target neutralizing antibodies against alternative lyssavirus species. The pmRFFIT enables high-throughput detection of rabies virus neutralizing antibodies in low-biocontainment settings and is suited to studies in wild or captive animals where large serum volumes cannot be obtained.


id: cord-102908-sr7j8z9c
author: Mersmann, Sophia F.
date: 2020-07-24
txt: ./txt/cord-102908-sr7j8z9c.txt
cache: ./cache/cord-102908-sr7j8z9c.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1101/2020.07.23.217745
doi: 10.1101/2020.07.23.217745
summary:
  We used differential binary labelling and statistical modelling to extract estimates of stoichiometry, our strategy is outlined in Figure 1 ; note that this approach can be generalised to apply to many other multi-component systems (i.e. how many protein x are found in assembly y?). As described above, our experimental design utilizes antibody labelled with spectrally distinct dyes allowing binary scoring of individual virus particles as positive if they interact with at least one Ab B molecule ( Figure 1 ). We have demonstrated quantitative analysis of 9C12 interaction with individual Adv particles ( Figure 3) ; we have confirmed that differential labelling of antibody does not bias binding ( Figure 4A & B) ; and that we could detect single molecules of 9C12 Biotin allowing discrimination of positive and negative AdV-9C12 complexes ( Figure 4C & D). However, using stoichiometric estimates to calibrate fluorescent data revealed population heterogeneity with a small proportion of virus particles binding ∼200 antibody molecules.

title:
  Learning to count: determining the stoichiometry of bio-molecular complexes using fluorescence microscopy and statistical modelling

abstract:
  Cellular biology occurs through myriad interactions between diverse molecular components, many of which assemble in to specific complexes. Various techniques can provide a qualitative survey of which components are found in a given complex. However, quantitative analysis of the absolute number of molecules within a complex (known as stoichiometry) remains challenging. Here we provide a novel method that combines fluorescence microscopy and statistical modelling to derive accurate molecular counts. We have devised a system in which a given biomolecule is differentially labelled with spectrally distinct fluorescent dyes (label A or B), which are then mixed such that B-labelled molecules are vastly outnumbered by those with label A. Complexes, containing this component, are then simply scored as either being positive or negative for label B. The frequency of positive complexes is directly related to the stoichiometry of interaction and molecular counts can be inferred by statistical modelling. We demonstrate this method using complexes of Adenovirus particles and monoclonal antibodies, achieving counts that are in excellent agreement with previous estimates. Beyond virology, this approach is readily transferable to other experimental systems and, therefore, provides a powerful tool for quantitative molecular biology. The statistical models used in our analysis are available here: https://github.com/sophiamersmann/molecular-counting, the raw data used for molecular counting can be found here: 10.5281/zenodo.3955142.


id: cord-103077-sh4w2mye
author: Lu, Shuai
date: 2020-10-16
txt: ./txt/cord-103077-sh4w2mye.txt
cache: ./cache/cord-103077-sh4w2mye.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1101/2020.10.15.339168
doi: 10.1101/2020.10.15.339168
summary:
  In this article, we propose a method to identify which amino acid residues of an antibody directly interact with its associated antigen based on the features from sequence and structure. Our algorithm uses convolution neural networks (CNNs) linked with graph convolution networks (GCNs) to make use of information from both sequential and spatial neighbors to understand more about the local environment of the target amino acid residue. According to the type of selecting neighbors of target residue for representing and predicting, the machine learning-based methods can be divided into two categories, leveraging sequential neighbors or spatial neighbors. And the stateof-art method [19] represented an antibody as a graph where each amino acid residue was a node and K nearest spatial neighbors were used in the convolution operator. In this work, we utilize the sequential and spatial neighbors of the target antibody residue by using Convolutional Neural Networks (CNNs) linked with Graph Neural Networks (GCNs) for paratope prediction.

title:
  Leveraging Sequential and Spatial Neighbors Information by Using CNNs Linked With GCNs for Paratope Prediction

abstract:
  Antibodies consisting of variable and constant regions, are a special type of proteins playing a vital role in immune system of the vertebrate. They have the remarkable ability to bind a large range of diverse antigens with extraordinary affinity and specificity. This malleability of binding makes antibodies an important class of biological drugs and biomarkers. In this article, we propose a method to identify which amino acid residues of an antibody directly interact with its associated antigen based on the features from sequence and structure. Our algorithm uses convolution neural networks (CNNs) linked with graph convolution networks (GCNs) to make use of information from both sequential and spatial neighbors to understand more about the local environment of the target amino acid residue. Furthermore, we process the antigen partner of an antibody by employing an attention layer. Our method improves on the state-of-the-art methodology.


id: cord-103255-4k13re9y
author: Daniell, Henry
date: 2001-05-01
txt: ./txt/cord-103255-4k13re9y.txt
cache: ./cache/cord-103255-4k13re9y.txt
extension: .txt
mime: text/plain
url: https://api.elsevier.com/content/article/pii/S1360138501019227
doi: 10.1016/s1360-1385(01)01922-7
summary:
  The production of recombinant proteins in plants has many potential advantages for generating biopharmaceuticals relevant to clinical medicine. In the decade since the expression and assembly of immunoglobulin (Ig) heavy and light chains into functional antibodies was first shown in transgenic tobacco, plants have proven to be versatile production systems for many forms of antibodies. Other advantages of tobacco include its relative ease of genetic manipulation, production of large numbers of seeds (up to a million per plant) and an impending need to explore alternate uses for this hazardous crop. However, the most attractive species for expressing subunit vaccine components should have high levels of soluble protein that is stable during storage; seed crops such as cereals are particularly suitable. Induction of a protective antibody response to foot and mouth disease in mice following oral or parenteral immunization with alfalfa transgenic plants expressing the viral structural protein VP1

title:
  Medical molecular farming: production of antibodies, biopharmaceuticals and edible vaccines in plants

abstract:
  Abstract The use of plants for medicinal purposes dates back thousands of years but genetic engineering of plants to produce desired biopharmaceuticals is much more recent. As the demand for biopharmaceuticals is expected to increase, it would be wise to ensure that they will be available in significantly larger amounts, on a cost-effective basis. Currently, the cost of biopharmaceuticals limits their availability. Plant-derived biopharmaceuticals are cheap to produce and store, easy to scale up for mass production, and safer than those derived from animals. Here, we discuss recent developments in this field and possible environmental concerns.


id: cord-103432-cdmoazrl
author: Richardson, Eve
date: 2020-06-02
txt: ./txt/cord-103432-cdmoazrl.txt
cache: ./cache/cord-103432-cdmoazrl.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1101/2020.06.02.121129
doi: 10.1101/2020.06.02.121129
summary:
  To test the ability of paratyping and clonotyping to group antibodies that target the same epitope we performed a test in a single-cell (paired VH/VL) data set of 1290 antibodies isolated from genetically engineered mice that have a full set of human immunoglobulin variable region genes [31] immunised with Pertussis toxoid (PTx). Each of the PTx-binders is referred to as a "probe" antibody; sequences that are within the same paratype or clonotype as the probe are predicted to bind PTx. The precision and recall of the two methods (calculated over the aggregate of predictions) for repertoire mining are comparable ( Figure 2 , Table 1 ). In a test system of transgenic mice immunised with Pertussis toxoid (PTx), we show for the first time that prediction and comparison of paratopes can be used to group antigen-specific antibodies in both an enriched, single-cell data set and non-enriched bulk heavy chain repertoires.

title:
  A computational method for immune repertoire mining that identifies novel binders from different clonotypes, demonstrated by identifying anti-Pertussis toxoid antibodies

abstract:
  Due to their shared genetic history, antibodies from the same clonotype often bind to the same epitope. This knowledge is used in immune repertoire mining, where known binders are used to search bulk sequencing repertoires to identify new binders. However current computational methods cannot identify epitope convergence between antibodies from different clonotypes, limiting the sequence diversity of antigen-specific antibodies which can be identified. We describe how the antibody binding site, the paratope, can be used to cluster antibodies with common antigen reactivity from different clonotypes. Our method, paratyping, uses the predicted paratope to identify these novel cross clonotype matches. We experimentally validated our predictions on a Pertussis toxoid dataset. Our results show that even the simplest abstraction of the antibody binding site, using only the length of the loops involved and predicted binding residues, is sufficient to group antigen-specific antibodies and provide additional information to conventional clonotype analysis.


id: cord-104226-bb4lyvhy
author: nan
date: 1992-09-01
txt: ./txt/cord-104226-bb4lyvhy.txt
cache: ./cache/cord-104226-bb4lyvhy.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2119354/
doi: nan
summary:
  The induction of monocyte/macrophage procoagulant activity (PCA) has been implicated in the pathogenesis of murine hepatitis virus strain 3 (MHV-3) infection and disease. The results reported here demonstrate that a neutralizing antibody to PCA protects animals from fulminant hepatitis and death associated with MHV-3 infection, and supports the notion that PCA is a potent inflammatory mediator that plays a pivotal role in the pathogenesis of liver injury resulting from MHV-3 infection. In contrast, mice infected with MHV-3 but treated with antibody to PCA showed a marked reduction in liver disease in all groups (25, 50 , and 100/.r ( were a few small loci of inflammatory cells with no necrosis (Fig. 2 D) . No fibrin was seen in the livers of infected mice treated with 100/~g of mAb. Treatment with anti-PCA alone resulted in no detectable histological evidence of liver disease in nonirLf~ed animals.

title:
  Monoclonal antiprothrombinase (3D4.3) prevents mortality from murine hepatitis virus (MHV-3) infection

abstract:
  The induction of monocyte/macrophage procoagulant activity (PCA) has been implicated in the pathogenesis of murine hepatitis virus strain 3 (MHV-3) infection and disease. Previously, we have shown that induction of PCA by MHV-3 correlated with resistance/susceptibility to infection in different mouse strains. In this study, all BALB/cJ mice that were infected with 10(3) plaque-forming units of MHV-3 developed severe liver disease and died within 96-120 h. Examination of the livers of these animals showed marked hepatic necrosis, deposition of fibrin, and cellular expression of PCA by direct immunofluorescence staining in areas of necrosis as well as in hepatic sinusoids. Splenic mononuclear cells recovered from these mice expressed high concentrations of PCA with time after infection. Infusion into mice of a high-titered monoclonal antibody that neutralized PCA (3D4.3) attenuated the development of hepatic necrosis and enhanced survival in a dose- dependent manner. All of the animals receiving 100 micrograms, and 44% and 22% of the animals that received 50 and 25 micrograms per day, respectively, survived for 10 d and made a full recovery. Administration of the antibody resulted in a dose-dependent reduction in fibrin deposition, PCA expression as detected by direct immunofluorescence staining and by a functional assay. In animals treated with high concentrations of antibody, titers of antibody to PCA fell from 87 +/- 15 micrograms/ml to 100 +/- 7 ng/ml during the active phase of the disease, consistent with sequestration due to binding of the immunoglobulin to cells expressing PCA. Surviving animals, when rechallenged with MHV-3, had a 40% mortality, consistent with the known rates of metabolism of immunoglobulin. This further suggested that protection was by a passive mechanism. The results reported here demonstrate that a neutralizing antibody to PCA protects animals from fulminant hepatitis and death associated with MHV-3 infection, and supports the notion that PCA is a potent inflammatory mediator that plays a pivotal role in the pathogenesis of liver injury resulting from MHV-3 infection.


id: cord-133453-23rfdkuw
title: Prediction and mitigation of mutation threats to COVID-19 vaccines and antibody therapies
author: Chen, Jiahui
date: 2020-10-13
txt: ./txt/cord-133453-23rfdkuw.txt
cache: ./cache/cord-133453-23rfdkuw.txt
extension: .txt
mime: text/plain
url: https://arxiv.org/pdf/2010.06357v1.pdf
doi: nan
summary:
  By integrating genetics, biophysics, deep learning, and algebraic topology, we deduce that some of the mutations such as M153I, S254F, and S255F may weaken the binding of S protein and antibodies, and potentially disrupt the efficacy and reliability of antibody therapies and vaccines in the development. The vaccination mechanism is to stimulate the primary immune response of the human body, which will activate T cells and B cells to generate the antibodies and long-lived memory cells that prevent infectious diseases, which is one of the most effective and economical means for combating with COVID-19 at this stage. Notably, understanding how mutations have changed the SARS-CoV-2 structure, function, infectivity, activity, and virulence is of great importance for coming up with life-saving strategies in virus control, containment, prevention, and medication, especially in the antibodies and vaccines development. Next, we study the BFE changes ∆∆G induced by 39 mutations on the SARS-CoV-2 S protein RBD for the antibody Fab 2-4 (PDB: 6XEY) in Figure 6 .

abstract:
  Antibody therapeutics and vaccines are among our last resort to end the raging COVID-19 pandemic.They, however, are prone to over 1,800 mutations uncovered by a Mutation Tracker. It is urgent to understand how vaccines and antibodies in the development would be impacted by mutations. In this work, we first study the mechanism, frequency, and ratio of mutations on the spike (S) protein, which is the common target of most COVID-19 vaccines and antibody therapies. Additionally, we build a library of antibody structures and analyze their 2D and 3D characteristics. Moreover, we predict the mutation-induced binding free energy (BFE) changes for the complexes of S protein and antibodies or ACE2. By integrating genetics, biophysics, deep learning, and algebraic topology, we deduce that some of the mutations such as M153I, S254F, and S255F may weaken the binding of S protein and antibodies, and potentially disrupt the efficacy and reliability of antibody therapies and vaccines in the development. We provide a strategy to prioritize the selection of mutations for designing vaccines or antibody cocktails.


id: cord-254531-pv55re2x
author: Mestecky, Jiri
date: 2009-06-04
txt: ./txt/cord-254531-pv55re2x.txt
cache: ./cache/cord-254531-pv55re2x.txt
extension: .txt
mime: text/plain
url: https://api.elsevier.com/content/article/pii/S0165247809000893
doi: 10.1016/j.imlet.2009.03.013
summary:
  In addition to mechanical barriers and a variety of innate defense factors, mucosal immunoglobulins (Igs) provide protection by two complementary mechanisms: specific antibody activity and innate, Ig glycan-mediated binding, both of which serve to contain the mucosal microbiota in its physiological niche. Bacteria Table 1 Examples of glycans as adhesion sites and receptors for selected bacteria and viruses that colonize, or infect, mucosal surfaces (adapted from [1, 26, 29, [60] [61] [62] [63] [64] [65] [66] [67] [68] [69] [70] [71] [72] [73] [74] [75] [76] [77] [78] 132] endogenous to the intestinal tract, oral cavity, and probably also the respiratory and genital tracts, are coated in vivo with S-IgA [9, 13, 17, [31] [32] [33] [34] [35] [36] [37] [38] [39] that limits their epithelial adherence and penetration, thereby confining them to the mucosal surfaces. Parallel structural and functional exploration of the principles of adaptive (specific antibody) and innate (glycan) S-IgA-mediated immunity is likely to generate novel approaches to the design of broadly protective compounds that work by selectively interfering with the adherence and penetration of pathogens, or that contain the commensal microbiota residing at mucosal surfaces.

title:
  Specific antibody activity, glycan heterogeneity and polyreactivity contribute to the protective activity of S-IgA at mucosal surfaces

abstract:
  An explanation of the principles and mechanisms involved in peaceful co-existence between animals and the huge, diverse, and ever-changing microbiota that resides on their mucosal surfaces represents a challenging puzzle that is fundamental in everyday survival. In addition to mechanical barriers and a variety of innate defense factors, mucosal immunoglobulins (Igs) provide protection by two complementary mechanisms: specific antibody activity and innate, Ig glycan-mediated binding, both of which serve to contain the mucosal microbiota in its physiological niche. Thus, the interaction of bacterial ligands with IgA glycans constitutes a discrete mechanism that is independent of antibody specificity and operates primarily in the intestinal tract. This mucosal site is by far the most heavily colonized with an enormously diverse bacterial population, as well as the most abundant production site for antibodies, predominantly of the IgA isotype, in the entire immune system. In embodying both adaptive and innate immune mechanisms within a single molecule, S-IgA maintains comprehensive protection of mucosal surfaces with economy of structure and function.


id: cord-254821-px4fe7mn
author: Infantino, Maria
date: 2020-05-10
txt: ./txt/cord-254821-px4fe7mn.txt
cache: ./cache/cord-254821-px4fe7mn.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/32330291/
doi: 10.1002/jmv.25932
summary:
  Sixty‐one COVID‐19 patients and 64 patients from a control group were tested by iFlash1800 CLIA analyzer for anti‐SARS CoV‐2 antibodies IgM and IgG. The more relaxed rules of the FDA''s "Policy for Diagnostic Tests for Coronavirus Disease-2019 during the Public Health Emergency" issued on 16 March 2020, 9 has allowed the market easier access to these tests as well as easier and faster diagnostics, but the lack of control in the production process is also dangerous making these tests potentially less reliable. 11 The aim of the this study was to assess the diagnostic performance of a novel fully automated CLIA for the quantitative detection of anti-SARS-CoV-2 IgM and IgG antibodies. 16 As with most existing studies on the diagnostic performance of the SARS-CoV-2 antibodies, our preliminary data showed that most COVID-19 patients have both IgM and IgG, and only few of them have isolated IgG or IgM antibodies. Development and clinical application of a rapid IgM-IgG combined antibody test for SARS-CoV-2 infection diagnosis Assessment of immune response to SARS-CoV-2 with fully-automated MAGLUMI 2019-nCoV IgG and IgM chemiluminescence immunoassays

title:
  Diagnostic accuracy of an automated chemiluminescent immunoassay for anti‐SARS‐CoV‐2 IgM and IgG antibodies: an Italian experience

abstract:
  A pandemic of coronavirus disease 2019 (COVID‐19) caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) has been spreading throughout the world. Though molecular diagnostic tests are the gold standard for COVID‐19, serological testing is emerging as a potential surveillance tool, in addition to its complementary role in COVID‐19 diagnostics. Indubitably quantitative serological testing provides greater advantages than qualitative tests but today there is still little known about serological diagnostics and what the most appropriate role quantitative tests might play. Sixty‐one COVID‐19 patients and 64 patients from a control group were tested by iFlash1800 CLIA analyzer for anti‐SARS CoV‐2 antibodies IgM and IgG. All COVID‐19 patients were hospitalized in San Giovanni di Dio Hospital (Florence, Italy) and had a positive oro/nasopharyngeal swab reverse‐transcription polymerase chain reaction result. The highest sensitivity with a very good specificity performance was reached at a cutoff value of 10.0 AU/mL for IgM and of 7.1 for IgG antibodies, hence near to the manufacturer's cutoff values of 10 AU/mL for both isotypes. The receiver operating characteristic curves showed area under the curve values of 0.918 and 0.980 for anti‐SARS CoV‐2 antibodies IgM and IgG, respectively. iFlash1800 CLIA analyzer has shown highly accurate results for the anti‐SARS‐CoV‐2 antibodies profile and can be considered an excellent tool for COVID‐19 diagnostics.


id: cord-255683-2eq24jth
title: Cross-Reactive Human IgM-Derived Monoclonal Antibodies that Bind to HIV-1 Envelope Glycoproteins
author: Chen, Weizao
date: 2010-02-04
txt: ./txt/cord-255683-2eq24jth.txt
cache: ./cache/cord-255683-2eq24jth.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/21755021/
doi: 10.3390/v2020547
summary:
  Ig Ms (IgMs) are on average significantly less divergent from germline antibodies and are relevant for the development of vaccine immunogens but are underexplored compared to IgGs. Here we describe the identification and characterization of several human IgM-derived mAbs against HIV-1 which were selected from a large phage-displayed naive human antibody library constructed from blood, lymph nodes and spleens of 59 healthy donors. To find whether the activity of the antibodies is related to antibody size and how the viral infection could be affected by cross-linking of HIV-1 Envs, we generated a single-chain Fv fragment (scFv) (scFv m19) of m19 and a human IgG1 Fc-fusion protein (m19Fc) of scFv m19; m19 was selected for further characterization because its light chain was relatively less divergent from the germline ( Figure 1b) and was the only one which did not contain any somatic mutations in the CDR3 of the light chain.

abstract:
  Elicitation of antibodies with potent and broad neutralizing activity against HIV by immunization remains a challenge. Several monoclonal antibodies (mAbs) isolated from humans with HIV-1 infection exhibit such activity but vaccine immunogens based on structures containing their epitopes have not been successful for their elicitation. All known broadly neutralizing mAbs (bnmAbs) are immunoglobulin (Ig) Gs (IgGs) and highly somatically hypermutated which could impede their elicitation. Ig Ms (IgMs) are on average significantly less divergent from germline antibodies and are relevant for the development of vaccine immunogens but are underexplored compared to IgGs. Here we describe the identification and characterization of several human IgM-derived mAbs against HIV-1 which were selected from a large phage-displayed naive human antibody library constructed from blood, lymph nodes and spleens of 59 healthy donors. These antibodies bound with high affinity to recombinant envelope glycoproteins (gp140s, Envs) of HIV-1 isolates from different clades. They enhanced or did not neutralize infection by some of the HIV-1 primary isolates using CCR5 as a coreceptor but neutralized all CXCR4 isolates tested although weakly. One of these antibodies with relatively low degree of somatic hypermutation was more extensively characterized. It bound to a highly conserved region partially overlapping with the coreceptor binding site and close to but not overlapping with the CD4 binding site. These results suggest the existence of conserved structures that could direct the immune response to non-neutralizing or even enhancing antibodies which may represent a strategy used by the virus to escape neutralizing immune responses. Further studies will show whether such a strategy plays a role in HIV infection of humans, how important that role could be, and what the mechanisms of infection enhancement are. The newly identified mAbs could be used as reagents to further characterize conserved non-neutralizing, weakly neutralizing or enhancing epitopes and modify or remove them from candidate vaccine immunogens.


id: cord-255936-hfa9w2dg
author: Jin, Junyeong
date: 2018-02-12
txt: ./txt/cord-255936-hfa9w2dg.txt
cache: ./cache/cord-255936-hfa9w2dg.txt
extension: .txt
mime: text/plain
url: https://api.elsevier.com/content/article/pii/S0006291X18301621
doi: 10.1016/j.bbrc.2018.01.141
summary:
  In this study, we tested this hypothesis by generating an antibody specific to the decoy epitope on the capsid protein of porcine circovirus type 2 (PCV2). To monitor the reactivity of sera to the CP 169e180 epitope, enzyme immunoassays, using BSA-conjugated CP 169e180 peptides and HRPconjugated anti-guinea pig IgG antibodies (Bethyl Laboratories), were performed as described previously. In a competition enzyme immunoassay employing a microtiter plate coated with BSA-conjugated CP 169e180 peptide and HRP-conjugated anti-porcine IgG antibody, the recombinant anti-CP 169e180 antibody almost completely inhibited the binding of naturally occurring anti-CP 169e180 antibody to the peptide in a PCV2-infected pig''s sera (Fig. 2) . In an enzyme immunoassay employing a microtiter plate coated with BSA-conjugated CP 169e180 peptide, sera from animals immunized with vaccine A had a significantly higher antibody titer than vaccine B-vaccinated animals (p < 0.01) (Fig. 3D) .

title:
  The level of decoy epitope in PCV2 vaccine affects the neutralizing activity of sera in the immunized animals

abstract:
  Abstract Viral pathogens have evolved a wide range of tactics to evade host immune responses and thus propagate effectively. One efficient tactic is to divert host immune responses toward an immunodominant decoy epitope and to induce non-neutralizing antibodies toward this epitope. Therefore, it is expected that the amount of decoy epitope in a subunit vaccine can affect the level of neutralizing antibody in an immunized animal. In this study, we tested this hypothesis by generating an antibody specific to the decoy epitope on the capsid protein of porcine circovirus type 2 (PCV2). Using this antibody, we found that two commercial vaccines contained statistically different amounts of the decoy epitope. The vaccine with lower levels of decoy epitope induced a significantly higher level of neutralizing antibody after immunization. This antibody can be used as an analytical tool to monitor the quality of a vaccine from batch to batch.


id: cord-256652-ent4vu3z
author: Tan, Joshua
date: 2018-03-19
txt: ./txt/cord-256652-ent4vu3z.txt
cache: ./cache/cord-256652-ent4vu3z.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1038/nm.4513
doi: 10.1038/nm.4513
summary:
  investigate this response at high resolution, we isolated IgM and IgG monoclonal antibodies from Tanzanian volunteers who were immunized by repeated injection of irradiated PfSPZ and who were found to be protected from controlled human malaria infection (CHMI) with infectious homologous PfSPZ. investigate this response at high resolution, we isolated IgM and IgG monoclonal antibodies from Tanzanian volunteers who were immunized by repeated injection of irradiated PfSPZ and who were found to be protected from controlled human malaria infection (CHMI) with infectious homologous PfSPZ. These findings, combined with data from peptide array experiments ( Supplementary Fig. 7) , identify the N-terminal junction binding site of the most potent neutralizing antibodies as including the first unit of the NANP repeat region and flanking non-repeat sequences, providing a molecular basis for the dual specificity of these antibodies.

title:
  A public antibody lineage that potently inhibits malaria infection by dual binding to the circumsporozoite protein

abstract:
  Immunization with attenuated Plasmodium falciparum sporozoites (PfSPZ) has been shown to be protective, but the features of the antibody response induced by this treatment remain unclear. To investigate this response at high resolution, we isolated IgM and IgG monoclonal antibodies from Tanzanian volunteers who were immunized by repeated injection of irradiated PfSPZ and who were found to be protected from controlled human malaria infection (CHMI) with infectious homologous PfSPZ. All IgG monoclonals isolated bound to P. falciparum circumsporozoite protein (PfCSP) and recognized distinct epitopes in the N-terminus, NANP repeat region, and C-terminus. Strikingly, the most effective antibodies, as assessed in a humanized mouse model, bound not only to the repeat region, but also to a minimal peptide at the PfCSP N-terminal junction that is not in the RTS,S vaccine. These dual-specific antibodies were isolated from different donors and used VH3-30 or VH3-33 alleles carrying tryptophan or arginine at position 52. Using structural and mutational data, we describe the elements required for germline recognition and affinity maturation. Our study provides potent neutralizing antibodies and relevant information for lineage-targeted vaccine design and immunization strategies.


id: cord-257465-9yrf7ofy
author: Finlay, William J. J.
date: 2016-05-23
txt: ./txt/cord-257465-9yrf7ofy.txt
cache: ./cache/cord-257465-9yrf7ofy.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/27730550/
doi: 10.1007/978-1-4939-6412-3_6
summary:
  These libraries are analogous to the naïve antibody repertoire in an animal, and selecting from them can result in the identifi cation of antibody fragments that exhibit high specifi city and occasionally high affi nity for the target protein. This process utilizes phage display for selection from germline targeting combinatorial libraries which results in the identifi cation of CDR residues amenable to human germ-lining without compromising on specifi city and affi nity. Nevertheless, phage display can be a relatively simple technology to use and when employed to harness natural repertoires of antibodies from immunized animals, it can offer a rapid path to highly specifi c, high-affi nity antibodies against problematic antigens . The immunized chickens appear to react to the proteins fully independently, as the phage display libraries generate individual scFv antibody clones that are fully specifi c by western blot and ELISA , showing no reactivity to their co-immunogens [ 37 , 59 ] .

title:
  Phage Display: A Powerful Technology for the Generation of High-Specificity Affinity Reagents from Alternative Immune Sources

abstract:
  Antibodies are critical reagents in many fundamental biochemical methods such as affinity chromatography, enzyme-linked immunosorbent assays (ELISA), flow cytometry, western blotting, immunoprecipitation, and immunohistochemistry techniques. As our understanding of the proteome becomes more complex, demand is rising for rapidly generated antibodies of higher specificity than ever before. It is therefore surprising that few investigators have moved beyond the classical methods of antibody production in their search for new reagents. Despite their long-standing efficacy, recombinant antibody generation technologies such as phage display are still largely the tools of biotechnology companies or research groups with a direct interest in protein engineering. In this chapter, we discuss the inherent limitations of classical polyclonal and monoclonal antibody generation and highlight an attractive alternative: generating high-specificity, high-affinity recombinant antibodies from alternative immune sources such as chickens, via phage display.


id: cord-260340-dujd28gg
title: Harnessing the immune system via FcγR function in immune therapy: a pathway to next‐gen mAbs
author: Chenoweth, Alicia M
date: 2020-04-12
txt: ./txt/cord-260340-dujd28gg.txt
cache: ./cache/cord-260340-dujd28gg.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1111/imcb.12326
doi: 10.1111/imcb.12326
summary:
  This is most evident for antibodies targeting cancer cells inducing antibody‐dependent killing or phagocytosis but is also true to some degree for the mAbs that neutralize or remove small macromolecules such as cytokines or other Igs. The use of mAb therapeutics has also revealed a "scaffolding" role for FcγR which, in different contexts, may either underpin the therapeutic mAb action such as immune agonism or trigger catastrophic adverse effects. Most therapeutic mAbs are IgG in origin and the heavy-chain subclass determines many of their biological properties including their long plasma half-life 3 ; complement activation, which is important in the action of some cytotoxic mAbs [4] [5] [6] and importantly engagement by their fragment crystallizable (Fc) region with specific cell surface receptors, called FccR, the subject of this review. Therapy with an IgG1 anti-cancer cell mAb may then be compromised by the inhibitory action of FccRIIb upon the ITAM signaling of the activating FccR as both types of receptor would be coengaged on such an effector cell by the mAb bound to the target cell.

abstract:
  The human fragment crystallizable (Fc)γ receptor (R) interacts with antigen‐complexed immunoglobulin (Ig)G ligands to both activate and modulate a powerful network of inflammatory host‐protective effector functions that are key to the normal physiology of immune resistance to pathogens. More than 100 therapeutic monoclonal antibodies (mAbs) are approved or in late stage clinical trials, many of which harness the potent FcγR‐mediated effector systems to varying degrees. This is most evident for antibodies targeting cancer cells inducing antibody‐dependent killing or phagocytosis but is also true to some degree for the mAbs that neutralize or remove small macromolecules such as cytokines or other Igs. The use of mAb therapeutics has also revealed a “scaffolding” role for FcγR which, in different contexts, may either underpin the therapeutic mAb action such as immune agonism or trigger catastrophic adverse effects. The still unmet therapeutic need in many cancers, inflammatory diseases or emerging infections such as severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) requires increased effort on the development of improved and novel mAbs. A more mature appreciation of the immunobiology of individual FcγR function and the complexity of the relationships between FcγRs and antibodies is fueling efforts to develop more potent “next‐gen” therapeutic antibodies. Such development strategies now include focused glycan or protein engineering of the Fc to increase affinity and/or tailor specificity for selective engagement of individual activating FcγRs or the inhibitory FcγRIIb or alternatively, for the ablation of FcγR interaction altogether. This review touches on recent aspects of FcγR and IgG immunobiology and its relationship with the present and future actions of therapeutic mAbs.


id: cord-261274-y74smbtd
title: Lactogenic immunity following vaccination of cattle with bovine coronavirus
author: Crouch, C. F
date: 2000-09-15
txt: ./txt/cord-261274-y74smbtd.txt
cache: ./cache/cord-261274-y74smbtd.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/10930672/
doi: 10.1016/s0264-410x(00)00177-8
summary:
  Abstract In order to investigate the ability of an oil adjuvanted vaccine containing bovine coronavirus antigen to enhance lactogenic immunity in the calf, pregnant cows and heifers were vaccinated and specific virus neutralising antibody levels determined in serum, colostrum and milk. Pre-existing antibody titres (as a result of natural infection) in the serum of these animals were found to be significantly increased as a result of a single shot vaccination carried out between 2 and 12 weeks before calving. This hypothesis was supported by the observations on the magnitude of the antibody titres found in the colostrum and milk of cows vaccinated at dierent times pre-calving with a vaccine containing 150 antigen units of BCoV. This report indicates that a single dose of coronavirus vaccine administered to the pregnant heifer 2 to 12 weeks before calving is capable of signi®cantly increasing the titre and duration of speci®c antibody present in colostrum and milk.

abstract:
  Abstract In order to investigate the ability of an oil adjuvanted vaccine containing bovine coronavirus antigen to enhance lactogenic immunity in the calf, pregnant cows and heifers were vaccinated and specific virus neutralising antibody levels determined in serum, colostrum and milk. Pre-existing antibody titres (as a result of natural infection) in the serum of these animals were found to be significantly increased as a result of a single shot vaccination carried out between 2 and 12 weeks before calving. This was reflected in a similar increase in the titre and duration of specific antibody in milk and colostrum that was passed on to the calves. The overall response observed was highly dependent on an adequate antigen payload being incorporated within the single dose vaccine. No abnormal local or systemic reactions were observed as a result of vaccination. It is hoped that this approach will lead to the production of a superior commercial vaccine for the protection of neonatal calves against enteric coronavirus infection.


id: cord-267015-mprsdi2e
author: Zhu, Zhongyu
date: 2008-03-15
txt: ./txt/cord-267015-mprsdi2e.txt
cache: ./cache/cord-267015-mprsdi2e.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/18271743/
doi: 10.1086/528801
summary:
  One of these antibodies, m102, which exhibited the highest level of cross-reactive neutralization of both NiV and HeV G, was affinity maturated by light-chain shuffling combined with random mutagenesis of its heavy-chain variable domain and panning against sG(HeV). We have previously identified neutralizing human monoclonal antibodies against Nipah virus (NiV) and Hendra virus (HeV) by panning a large nonimmune antibody library against a soluble form of the HeV attachment-envelope glycoprotein G (sG HeV ). One of these antibodies, m102, which exhibited the highest level of cross-reactive neutralization of both NiV and HeV G, was affinity maturated by light-chain shuffling combined with random mutagenesis of its heavychain variable domain and panning against sG HeV . To demonstrate that m102.4 measured in plasma was biologically active, serum collected on days 1, 4, and 8 was evaluated using virus neutralization assays, as described above (data not shown). Receptor binding, fusion inhibition, and induction of cross-reactive neutralizing antibodies by a soluble G glycoprotein of Hendra virus

title:
  Exceptionally Potent Cross-Reactive Neutralization of Nipah and Hendra Viruses by a Human Monoclonal Antibody

abstract:
  We have previously identified neutralizing human monoclonal antibodies against Nipah virus (NiV) and Hendra virus (HeV) by panning a large nonimmune antibody library against a soluble form of the HeV attachment-envelope glycoprotein G (sG(HeV)). One of these antibodies, m102, which exhibited the highest level of cross-reactive neutralization of both NiV and HeV G, was affinity maturated by light-chain shuffling combined with random mutagenesis of its heavy-chain variable domain and panning against sG(HeV). One of the selected antibody Fab clones, m102.4, had affinity of binding to sG(HeV) that was equal to or higher than that of the other Fabs; it was converted to IgG1 and tested against infectious NiV and HeV. It exhibited exceptionally potent and cross-reactive inhibitory activity with 50% inhibitory concentrations below 0.04 and 0.6 μg/mL, respectively. The virus-neutralizing activity correlated with the binding affinity of the antibody to sG(HeV) and sG(NiV). m102.4 bound a soluble form of NiV G (sG(NiV)) better than it bound sG(HeV), and it neutralized NiV better than HeV, despite being originally selected against sG(HeV). These results suggest that m102.4 has potential as a therapeutic agent for the treatment of diseases caused by henipaviruses. It could be also used for prophylaxis and diagnosis, and as a research reagent


id: cord-267601-3ahmyicn
title: Passive Immunization: Systemic and Mucosal
author: Renegar, Kathryn B.
date: 2007-05-09
txt: ./txt/cord-267601-3ahmyicn.txt
cache: ./cache/cord-267601-3ahmyicn.txt
extension: .txt
mime: text/plain
url: https://www.sciencedirect.com/science/article/pii/B9780124915435500504
doi: 10.1016/b978-012491543-5/50050-4
abstract: nan
summary:
  Both rats and mice can actively transport IgG from the gut into the serum for approximately 2 weeks (see Combined Prenatal and Postnatal Transfer earlier in this chapter); thus, observed protection could be due either to antibody in the milk bathing the mucosal surfaces or to maternal antibody being transported into the serum and secretions of the offspring. Only a limited number of studies on the transport of antibodies into respiratory secretions have been reported, but the results have shown that selective transport of passively administered serum IgA into the respiratory tract is possible in sheep and mice. (1994) determined that passively administered monoclonal pIgA isotype-switch variants, generated from IgG hybridomas producing antibodies specific for bacterial respiratory tract pathogens, were selectively transported relative to IgG into both the upper and lower respiratory tract secretions of mice. To determine whether intravenously administered pIgA antiinfluenza monoclonal antibody could mediate protection against local influenza virus challenge, passively immunized mice were challenged intranasally while awake with influenza virus.


id: cord-267736-rya9w6sh
title: Development of an ELISA-array for simultaneous detection of five encephalitis viruses
author: Kang, Xiaoping
date: 2012-02-27
txt: ./txt/cord-267736-rya9w6sh.txt
cache: ./cache/cord-267736-rya9w6sh.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/22369052/
doi: 10.1186/1743-422x-9-56
summary:
  The ELISA-array assay is based on a "sandwich" ELISA format and consists of viral antibodies printed directly on 96-well microtiter plates, allowing for direct detection of 5 viruses. The developed ELISA-array proved to have similar specificity and higher sensitivity compared with the conventional ELISAs. This method was validated by different viral cultures and three chicken eggs inoculated with infected patient serum. The results demonstrated that this method combined the advantage of ELISA and protein array (multiplex and ease of use) and has potential for the identification of clinical encephalitis virus. When spotting, different spotting buffers and concentrations of capture monoclonal antibodies were evaluated to optimize the ELISA-array assay. To verify the results tested by ELISA-array, RNA extracted from chicken eggs was applied to a real time-RT-PCR assay using primers and probes targeting TBEV. In this study, we developed a multiplex ELISA-based method in a double-antibody sandwich format for the simultaneous detection of five encephalitis-associated viral pathogens.

abstract:
  Japanese encephalitis virus(JEV), tick-borne encephalitis virus(TBEV), and eastern equine encephalitis virus (EEEV) can cause symptoms of encephalitis. Establishment of accurate and easy methods by which to detect these viruses is essential for the prevention and treatment of associated infectious diseases. Currently, there are still no multiple antigen detection methods available clinically. An ELISA-array, which detects multiple antigens, is easy to handle, and inexpensive, has enormous potential in pathogen detection. An ELISA-array method for the simultaneous detection of five encephalitis viruses was developed in this study. Seven monoclonal antibodies against five encephalitis-associated viruses were prepared and used for development of the ELISA-array. The ELISA-array assay is based on a "sandwich" ELISA format and consists of viral antibodies printed directly on 96-well microtiter plates, allowing for direct detection of 5 viruses. The developed ELISA-array proved to have similar specificity and higher sensitivity compared with the conventional ELISAs. This method was validated by different viral cultures and three chicken eggs inoculated with infected patient serum. The results demonstrated that the developed ELISA-array is sensitive and easy to use, which would have potential for clinical use.


id: cord-267744-asjvf123
title: Chicken single-chain variable fragments against the SARS-CoV spike protein
author: Lee, Yu-Ching
date: 2007-07-23
txt: ./txt/cord-267744-asjvf123.txt
cache: ./cache/cord-267744-asjvf123.txt
extension: .txt
mime: text/plain
url: https://api.elsevier.com/content/article/pii/S0166093407002236
doi: 10.1016/j.jviromet.2007.06.010
summary:
  Following the immunization of chickens with these recombinant spike proteins, two single-chain variable fragment (scFv) antibody libraries were established with short or long linkers to contain 5 × 10(7) and 9 × 10(6) transformants, respectively. In a comparison of nucleotide sequences with the chicken germline gene, we found that all clones varied in the complementarity-determining regions, that two scFv antibodies reacted significantly with SARS-CoV-infected Vero cells, and that those two specific scFv antibodies recognized the same region of the spike protein spanning amino acid residues 750–1000. The current study aimed to show that monoclonal IgY scFv antibodies which bind specifically to the S protein and SARS-CoV-infected Vero cells can be isolated from chickens immunized with Escherichia coli-derived S proteins. Cellular lysates containing single-chain variable fragment (scFv) antibodies from various Ssc (A) and Lsc (B) library clones were examined for their binding to SARS-CoV-infected cell lysates using a commercially available kit.

abstract:
  The major concern for severe acute respiratory syndrome (SARS), caused by the SARS-associated coronavirus (SARS-CoV), is the lack of diagnostic and therapeutic agents. Using a phage display technology in a chicken system, high-affinity monoclonal antibody fragments against the SARS-CoV spike protein were characterized. Ten truncated spike protein gene fragments were expressed in Escherichia coli cells. Following the immunization of chickens with these recombinant spike proteins, two single-chain variable fragment (scFv) antibody libraries were established with short or long linkers to contain 5 × 10(7) and 9 × 10(6) transformants, respectively. After four rounds of panning selection, the scFv antibodies of randomly chosen clones were demonstrated by Coomassie blue staining, and verified by western blot analysis. In a comparison of nucleotide sequences with the chicken germline gene, we found that all clones varied in the complementarity-determining regions, that two scFv antibodies reacted significantly with SARS-CoV-infected Vero cells, and that those two specific scFv antibodies recognized the same region of the spike protein spanning amino acid residues 750–1000. In conclusion, the results suggest that the chicken scFv phage display system can be a potential model for mass production of high-affinity antibodies against the SARS-CoV spike protein.


id: cord-268417-6eyetb5i
title: Neutralization of Animal Viruses
author: Mandel, Benjamin
date: 1978-12-31
txt: ./txt/cord-268417-6eyetb5i.txt
cache: ./cache/cord-268417-6eyetb5i.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/107731/
doi: 10.1016/s0065-3527(08)60101-3
summary:
  Somewhat earlier, Morgan (1945''1 had reported that discrepancies in the quantitative aspects of the neutralization of WEE virus by immune rabbit sera were related to the use of fresh or heated serum, and that the addition of complement to the latter tended to eliminate the discrepancies. Further studies (Radwan et al., 1973) showed that the addition of complement to virus complexed with dependent antibody eventually resulted in lysis of the viral membrane. It was also shown (Yoshino and Taniguchi, 1966 ) that antibodies induced in guinea pigs by immunization, and in humans following herpes infection, were initially dependent and later independent of complement for neutralizing activity. A relevant observation has been made in several studies; neutralization of infectious virus-antibody complexes by antiglobulin also shows a single-hit mechanism, and at a rate that exceeds the rate of the homotypic reaction.

abstract:
  Publisher Summary Various aspects of the interaction of bacterial viruses and antibody were studied by Andrewes and Elford in England. Similar studies, as well as studies on animal viruses, were carried out in Australia by Burnet and his colleagues. One result of their extensive studies, which were summarized in great detail, was the conclusion that, with respect to their interaction with antibody, bacterial and animal viruses were basically different. Specifically, the difference resided in the stability of the union of virus and antibody, whereas bacterial viruses formed stable complexes, animal viruses formed complexes that tended to dissociate readily. The introduction of animal cell cultures as host systems greatly aided in the study of animal viruses, with respect to fewer and more readily controlled variables, and by the use of the plaque assay in enhanced quantitative reliability. In 1956, Dulbecco et al. described the interaction of two animal viruses with their respective antibodies. The results of these studies led these investigators to conclude, among other things, that animal viruses, at least the two they studied, reacted with antibodies to form complexes that did not dissociate spontaneously. This interpretation was challenged by Fazekas de St. Groth and Reid. As more animal virus-antibody systems were studied by many investigators, there seemed to be a greater accord for irreversible, rather than reversible, interaction. For this reason, in this chapter it is assumed that there are no differences between bacterial viruses, as one category, and animal viruses, as a separate category, concerning their interaction with antibodies. Rather, differences, when they exist, are considered to be related to the viruses per se. Although this chapter is intended to survey the neutralization of animal viruses, occasional reference is made to the studies on bacterial viruses when these studies are pertinent and illuminating to the topic at hand.


id: cord-269023-g21a9ik2
title: Before Virus, After Virus: A Reckoning
author: Mukherjee, Siddhartha
date: 2020-10-15
url: https://www.ncbi.nlm.nih.gov/pubmed/33064987/
doi: 10.1016/j.cell.2020.09.042
abstract:
  The 2020 Lasker Awards, a celebration of one of the most prestigious international prizes given to individuals for extraordinary contributions to Basic and Clinical Medical Research, Pubic Health, and Special Achievement, was cancelled because of the COVID-19 pandemic. Typically, essays on the awardees and their scientific and medical contributions are solicited and published in Cell in collaboration with the Lasker Committee. This year, the Lasker Committee commissioned an essay to reflect on the historic contributions that scientists and physicians have made to our understanding of immunology and virology, and future directions in medical and basic research that have been highlighted by COVID-19 pandemic.


id: cord-274557-2071770h
title: On the Dark Side of Therapies with Immunoglobulin Concentrates: The Adverse Events
author: Späth, Peter J.
date: 2015-02-05
txt: ./txt/cord-274557-2071770h.txt
cache: ./cache/cord-274557-2071770h.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/25699039/
doi: 10.3389/fimmu.2015.00011
summary:
  i.e., cold-ethanol or ion-exchange chromatography, contaminants, route of application, i.e., intra muscular (IMIG), intravenous (IVIG), or subcutaneous (SCIG), the rate of increase of the exogenous IgG in the circulation of the recipient over time and, last but not least an eventually existing risk factor from patients'' side ( Figure 1 ) as well as incorrect handling of the concentrate are factors having a role in inducing non-infectious AEs related to administration of IgG concentrates ( Table 1) . The complement-mediated AEs were considered to be caused by aggregates in the product ("spontaneous complement activation" or anti-complementary activity or ACA) or by in vivo formation of immune complexes (ICs, patient''s condition related; e.g., subclinical infections or the unnoticed presence of anti-IgA antibodies) and therefore only IgG concentrates with low or absent ACA is accepted by authorities for human use.

abstract:
  Therapy by human immunoglobulin G (IgG) concentrates is a success story ongoing for decades with an ever increasing demand for this plasma product. The success of IgG concentrates on a clinical level is documented by the slowly increasing number of registered indication and the more rapid increase of the off-label uses, a topic dealt with in another contribution to this special issue of Frontiers in Immunology. A part of the success is the adverse event (AE) profile of IgG concentrates which is, even at life-long need for therapy, excellent. Transmission of pathogens in the last decade could be entirely controlled through the antecedent introduction by authorities of a regulatory network and installing quality standards by the plasma fractionation industry. The cornerstone of the regulatory network is current good manufacturing practice. Non-infectious AEs occur rarely and mainly are mild to moderate. However, in recent times, the increase in frequency of hemolytic and thrombotic AEs raised worrying questions on the possible background for these AEs. Below, we review elements of non-infectious AEs, and particularly focus on hemolysis and thrombosis. We discuss how the introduction of plasma fractionation by ion-exchange chromatography and polishing by immunoaffinity chromatographic steps might alter repertoire of specificities and influence AE profiles and efficacy of IgG concentrates.


id: cord-274756-nnm1n09a
title: Human immunology and immunotherapy: main achievements and challenges
author: Varadé, Jezabel
date: 2020-09-02
txt: ./txt/cord-274756-nnm1n09a.txt
cache: ./cache/cord-274756-nnm1n09a.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/32879472/
doi: 10.1038/s41423-020-00530-6
summary:
  The development of different types of immunotherapies, including vaccines (prophylactic and therapeutic), and the use of pathogens, monoclonal antibodies, recombinant proteins, cytokines, and cellular immunotherapies, are changing the way in which we approach many diseases, especially cancer. In addition to those showing the essential role of LTi cells in the formation of secondary lymphoid organs during embryogenesis and the postnatal development of intestinal lymphoid clusters, recent studies also provide evidence that subsets of ILCs express multiple factors that modulate the adaptive immune response in health and disease 27, 28 . Autoimmunity: In the case of therapeutic vaccines for autoimmune diseases, such as multiple sclerosis, diabetes, Myasthenia gravis or Guillain Barré syndrome, the intention is to induce tolerance to self-antigens through the activation of regulatory cells (Tregs and Bregs) and tolerogenic dendritic cells, thus avoiding the immune response to self-components 211 .

abstract:
  The immune system is a fascinating world of cells, soluble factors, interacting cells, and tissues, all of which are interconnected. The highly complex nature of the immune system makes it difficult to view it as a whole, but researchers are now trying to put all the pieces of the puzzle together to obtain a more complete picture. The development of new specialized equipment and immunological techniques, genetic approaches, animal models, and a long list of monoclonal antibodies, among many other factors, are improving our knowledge of this sophisticated system. The different types of cell subsets, soluble factors, membrane molecules, and cell functionalities are some aspects that we are starting to understand, together with their roles in health, aging, and illness. This knowledge is filling many of the gaps, and in some cases, it has led to changes in our previous assumptions; e.g., adaptive immune cells were previously thought to be unique memory cells until trained innate immunity was observed, and several innate immune cells with features similar to those of cytokine-secreting T cells have been discovered. Moreover, we have improved our knowledge not only regarding immune-mediated illnesses and how the immune system works and interacts with other systems and components (such as the microbiome) but also in terms of ways to manipulate this system through immunotherapy. The development of different types of immunotherapies, including vaccines (prophylactic and therapeutic), and the use of pathogens, monoclonal antibodies, recombinant proteins, cytokines, and cellular immunotherapies, are changing the way in which we approach many diseases, especially cancer.


id: cord-275402-z92b18mb
author: Diamant, Eran
date: 2015-05-29
url: https://doi.org/10.3390/toxins7061854
doi: 10.3390/toxins7061854
title:
  Monoclonal Antibody Combinations that Present Synergistic Neutralizing Activity: A Platform for Next-Generation Anti-Toxin Drugs

abstract:
  Monoclonal antibodies (MAbs) are among the fastest-growing therapeutics and are being developed for a broad range of indications, including the neutralization of toxins, bacteria and viruses. Nevertheless, MAbs potency is still relatively low when compared to conventional polyclonal Ab preparations. Moreover, the efficacy of an individual neutralizing MAb may significantly be hampered by the potential absence or modification of its target epitope in a mutant or subtype of the infectious agent. These limitations of individual neutralizing MAbs can be overcome by using oligoclonal combinations of several MAbs with different specificities to the target antigen. Studies conducted in our lab and by others show that such combined MAb preparation may present substantial synergy in its potency over the calculated additive potency of its individual MAb components. Moreover, oligoclonal preparation is expected to be better suited to compensating for reduced efficacy due to epitope variation. In this review, the synergistic neutralization properties of combined oligoclonal Ab preparations are described. The effect of Ab affinity, autologous Fc fraction, and targeting a critical number of epitopes, as well as the unexpected contribution of non-neutralizing clones to the synergistic neutralizing effect are presented and discussed.


id: cord-275946-ofd2ipvs
title: Serodiagnostics for Severe Acute Respiratory Syndrome–Related Coronavirus-2: A Narrative Review
author: Cheng, Matthew P.
date: 2020-06-04
txt: ./txt/cord-275946-ofd2ipvs.txt
cache: ./cache/cord-275946-ofd2ipvs.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.7326/m20-2854
doi: 10.7326/m20-2854
summary:
  Accurate serologic tests to detect host antibodies to severe acute respiratory syndrome–related coronavirus-2 (SARS-CoV-2) will be critical for the public health response to the coronavirus disease 2019 pandemic. This article discusses key use cases for SARS-CoV-2 antibody detection tests and their application to serologic studies, reviews currently available assays, highlights key areas of ongoing research, and proposes potential strategies for test implementation. Appropriately designed seroepidemiologic studies will play an essential part in the public health response to the COVID-19 pandemic by characterizing transmission dynamics, refining disease burden estimates, and providing insight into the kinetics of humoral immunity to SARS-CoV-2. Serologic surveillance studies can also assess the accumulation of persons with antibody responses over time to estimate incidence of SARS-CoV-2 infection (57, 58) and can track age-and jurisdiction-specific disease susceptibility and identify at-risk populations (59) .

abstract:
  Accurate serologic tests to detect host antibodies to severe acute respiratory syndrome–related coronavirus-2 (SARS-CoV-2) will be critical for the public health response to the coronavirus disease 2019 pandemic. Many use cases are envisaged, including complementing molecular methods for diagnosis of active disease and estimating immunity for individuals. At the population level, carefully designed seroepidemiologic studies will aid in the characterization of transmission dynamics and refinement of disease burden estimates and will provide insight into the kinetics of humoral immunity. Yet, despite an explosion in the number and availability of serologic assays to test for antibodies against SARS-CoV-2, most have undergone minimal external validation to date. This hinders assay selection and implementation, as well as interpretation of study results. In addition, critical knowledge gaps remain regarding serologic correlates of protection from infection or disease, and the degree to which these assays cross-react with antibodies against related coronaviruses. This article discusses key use cases for SARS-CoV-2 antibody detection tests and their application to serologic studies, reviews currently available assays, highlights key areas of ongoing research, and proposes potential strategies for test implementation.


id: cord-277076-yvsyo4l9
title: SARS
author: Berger, A.
date: 2019-09-12
txt: ./txt/cord-277076-yvsyo4l9.txt
cache: ./cache/cord-277076-yvsyo4l9.txt
extension: .txt
mime: text/plain
url: https://api.elsevier.com/content/article/pii/B9780444639516006240
doi: 10.1016/b978-0-444-63951-6.00624-0
summary:
  Measures including source isolation of patientswho only became infectious after onset of clinical symptomsstrict infection control in health care facilities, timely identification and quarantining of exposed contacts, and perhaps also measures to increase social distance, such as travel warnings and screening of travelers, had led to this remarkable and remarkably rapid success. A further, small SARS outbreak occurred again in Guangdong in late 2003/early 2004; molecular analysis of virus isolates from human cases and animals sampled at the same place and time confirmed that this was zoonotically acquired from Paguma larvata. The laboratory diagnosis of SARS remains a challenge; in fact, despite the rapid identification of SARS-CoV as the etiological agent, testing contributed little to the successful control of the 2003 outbreak. A negative antibody test result later than 21 days after the onset of illness is likely to indicate that no infection with SARS-CoV has taken place.

abstract:
  Severe acute respiratory syndrome (SARS) emerged in southern China in late 2002. It first spread within Guangdong Province and then to other parts of China. Via air travelers, it quickly reached various countries around the globe, causing several major hospital outbreaks. Within weeks, the causative agent, a previously unknown coronavirus (SARS-CoV), was identified, thanks to an unprecedented international effort led by the World Health Organization (WHO). Its origin was quickly traced to wild animals traded locally for culinary purposes. Masked palm civet and some other species seem to have acted as intermediate hosts. Since then, SARS-like coronaviruses were found in different bat species in China and elsewhere, and bats are now regarded as the wildlife reservoir for SARS-CoV. Fortunately, the SARS outbreak could be contained within months. Until July 2003, it had caused 8096 cases, with 774 deaths. Once adequate measures such as isolating patients and quarantining their contacts were strictly adhered to, further transmission between human beings could be interrupted. SARS is an example of how rapidly an infectious agent can spread in the modern world. At the same time, it should serve as a showcase of how international cooperation and modern science can help to combat the spread of infectious diseases.


id: cord-277894-0qw0t78s
title: Canine coronavirus in Australian dogs
author: NAYLOR, MJ
date: 2008-03-10
txt: ./txt/cord-277894-0qw0t78s.txt
cache: ./cache/cord-277894-0qw0t78s.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/11256282/
doi: 10.1111/j.1751-0813.2001.tb10718.x
summary:
  Objective To estimate the frequency of serum antibodies (IgG and IgM) to canine coronavirus (CCV) in the Australian dog population and evaluate the role of CCV as a causative agent of gastroenteritis. Of those dogs that were presented with clinical signs of gastroenteritis such as diarrhoea and vomiting(n = 29), 85% were positive in the IgM ELISA and 85.7% in the IgG ELISA for antibodies to CCV. In this study we determine the prevalence of serum IgG and IgM antibodies to CCV from a larger number of dogs sampled from throughout Australia. 7, 8 In the open population of 1107 dogs tested we found 15.8% positive for anti-CCV IgG antibody, which reflects past exposure and infection with CCV whereas the electron microscopic studies detected only those dogs currently infected and shedding virus in their faeces.

abstract:
  Objective To estimate the frequency of serum antibodies (IgG and IgM) to canine coronavirus (CCV) in the Australian dog population and evaluate the role of CCV as a causative agent of gastroenteritis. Design A serological survey of antibodies to CCV among different dog populations. Procedure The development and characterisation of an indirect ELISA for the detection of antibodies (IgG and IgM) to CCV was undertaken. Sera collected from both diarrhoeal and non‐diarrhoeal dogs from various populations throughout Australia were tested for these antibodies to CCV. Results Serum samples (1396) collected from 1984 to 1998 were tested for the presence of IgG antibodies to CCV. Samples were divided into two categories on the basis of the number of dogs housed together. The groups were either an open population containing dogs housed as groups of three or less, or kennel populations. Sera from 15.8% of the open population and 40.8% of kennelled dogs were positive for CCV antibodies. The prevalence of antibodies varied from zero to 76% in kennelled dogs. About 23% of 128 dogs positive for IgG antibodies to CCV were also positive for IgM antibodies to CCV, indicating recent CCV infection. Of those dogs that were presented with clinical signs of gastroenteritis such as diarrhoea and vomiting(n = 29), 85% were positive in the IgM ELISA and 85.7% in the IgG ELISA for antibodies to CCV. In comparison, for those dogs presented without any history of gastroenteritis only 15% were positive for IgM and 30% positive for IgG. Conclusion Serological evidence indicates that infection with CCV in dogs is widespread throughout the Australian mainland. The prevalence of antibodies varies greatly among different populations, with an average of 40.8% positive in kennelled populations and 15.8% in the open population.


id: cord-278281-bdoavpsb
title: Antibody response to equine coronavirus in horses inoculated with a bovine coronavirus vaccine
author: NEMOTO, Manabu
date: 2017-10-06
txt: ./txt/cord-278281-bdoavpsb.txt
cache: ./cache/cord-278281-bdoavpsb.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/28993568/
doi: 10.1292/jvms.17-0414
summary:
  Virus neutralization tests showed that antibody titers against ECoV increased in all six horses tested at 14 days post inoculation, although the antibody titers were lower against ECoV than against BCoV. The virus-neutralizing antibody titers of horses inoculated with 1 or 2 ml of the BCoV vaccine are shown in Table 1 . In horses inoculated with 1 ml of vaccine, the geometric mean antibody titers against BCoV at 0, 7, 14, 28, 42 and 56 dpi were 4, 5, 32, 102, 645 and 323, respectively, and the geometric mean antibody titers against ECoV were 4, 6, 20, 25, 40 and 51 (Table 1) . Nevertheless, the antibody titers of all vaccinated horses in the present study were no more than 128, and we therefore consider that the BCoV vaccine will have limited efficacy against ECoV infection in horses.

abstract:
  A vaccine for equine coronavirus (ECoV) is so far unavailable. Bovine coronavirus (BCoV) is antigenically related to ECoV; it is therefore possible that BCoV vaccine will induce antibodies against ECoV in horses. This study investigated antibody response to ECoV in horses inoculated with BCoV vaccine. Virus neutralization tests showed that antibody titers against ECoV increased in all six horses tested at 14 days post inoculation, although the antibody titers were lower against ECoV than against BCoV. This study showed that BCoV vaccine provides horses with antibodies against ECoV to some extent. It is unclear whether antibodies provided by BCoV vaccine are effective against ECoV, and therefore ECoV challenge studies are needed to evaluate efficacy of the vaccine in the future.


id: cord-279105-e2zjxjox
title: Serological Approaches for COVID-19: Epidemiologic Perspective on Surveillance and Control
author: Lee, Cheryl Yi-Pin
date: 2020-04-24
txt: ./txt/cord-279105-e2zjxjox.txt
cache: ./cache/cord-279105-e2zjxjox.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/32391022/
doi: 10.3389/fimmu.2020.00879
summary:
  With the limitations of qRT-PCR, immunoassays may offer another FIGURE 2 | Schematic illustration on the window period of detection for either viral RNA or antibodies in SARS-CoV-2-infected individuals. However, interestingly, one study demonstrated that longitudinal profiling of both antibodies in a population of 63 COVID-19 patients showed no specific chronological order in terms of IgM and IgG seroconversion (10) , which was also observed in patients infected with SARS-CoV and another human coronavirus, Middle East Respiratory Syndrome coronavirus (MERS-CoV) (22, 23) . These findings on SARS-CoV-2-specific antibodies seroconversion against the S viral protein suggest the importance to test for both IgM and IgG antibodies to confirm a positive infection. With the availability of immunoassays utilizing various coronavirus structural proteins, the use of more than one different antigen-based serological approach may be essential to establish a true positive SARS-CoV-2 infection.

abstract:
  Since December 2019, the novel coronavirus, SARS-CoV-2, has garnered global attention due to its rapid transmission, which has infected more than two million people worldwide. Early detection of SARS-CoV-2 is one of the crucial interventions to control virus spread and dissemination. Molecular assays have been the gold standard to directly detect for the presence of viral genetic material in infected individuals. However, insufficient viral RNA at the point of detection may lead to false negative results. As such, it is important to also employ immune-based assays to determine one's exposure to SARS-CoV-2, as well as to assist in the surveillance of individuals with prior exposure to SARS-CoV-2. Within a span of 4 months, extensive studies have been done to develop serological systems to characterize the antibody profiles, as well as to identify and generate potentially neutralizing antibodies during SARS-CoV-2 infection. The vast diversity of novel findings has added value to coronavirus research, and a strategic consolidation is crucial to encompass the latest advances and developments. This review aims to provide a concise yet extensive collation of current immunoassays for SARS-CoV-2, while discussing the strengths, limitations and applications of antibody detection in SARS-CoV-2 research and control.


id: cord-281760-34wuttqw
title: Egg yolk antibodies (IgY) and their applications in human and veterinary health: A review
author: Pereira, E.P.V.
date: 2019-05-22
txt: ./txt/cord-281760-34wuttqw.txt
cache: ./cache/cord-281760-34wuttqw.txt
extension: .txt
mime: text/plain
url: https://api.elsevier.com/content/article/pii/S1567576919302206
doi: 10.1016/j.intimp.2019.05.015
summary:
  Considering the fast development of IgY technology, this work aims to review its applications in human and animal health, in addition to increasing the potential use of these antibodies among researchers and consequently promoting the reduced use of non-invasive procedures on animals. extracted IgY from hens immunized with the recombinant protein FanC, from enterotoxigenic Escherichia coli (ETEC) and these antibodies bound specifically to FanC in ELISA, Western blot and Dot-blotting [59] , demanding, thus, more investigations to evaluate its viability as a potential immunotherapeutic compound. Anti-DENV2 IgY produced in goose was able to neutralize the virus in vitro and in vivo without binding to Fcγ receptors on myeloid cells and generating ADE (antibody dependent enhancement) in mice [57] . Hen egg yolk antibodies (IgY), production and use for passive immunization against bacterial enteric infections in chicken: a review Preventive effect of anti-VacA egg yolk immunoglobulin (IgY) on Helicobacter pylori-infected mice

abstract:
  Egg yolk constitutes a relevant alternative source of antibodies. It presents some advantages over mammalian serum immunoglobulins regarding productivity, animal welfare and specificity. The main immunoglobulin present in avian blood (IgY) is transmitted to their offspring and accumulates in egg yolks, which enables the non-invasive harvesting of high amounts of antibodies. Moreover, due to structural differences and phylogenetic distance, IgY is more suitable for diagnostic purposes than mammalian antibodies, since it does not react with certain components of the human immune system and displays greater avidity for mammalian conserved proteins. IgY has been extensively used in health researches, as both therapeutic and diagnostic tool. This article aims to review its applications in both human and veterinary health.


id: cord-282081-qaagup4d
title: Nanobodies—Useful Tools for Allergy Treatment?
author: Flicker, Sabine
date: 2020-09-30
txt: ./txt/cord-282081-qaagup4d.txt
cache: ./cache/cord-282081-qaagup4d.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.3389/fimmu.2020.576255
doi: 10.3389/fimmu.2020.576255
summary:
  Their superior properties such as chemical stability, high affinity to a broad spectrum of epitopes, low immunogenicity, ease of their generation, selection and production proved nanobodies also to be remarkable to investigate their efficacy for passive treatment of type I allergy, an exaggerated immune reaction to foreign antigens with increasing global prevalence. Similar to the evaluation of conventional antibodies with the focus to identify effective protective monoclones, generated nanobodies have to be assessed first for their allergen specificity, epitope recognition, cross-reactivity to homologous allergens present in related species, for their affinity to their corresponding allergens and most importantly for their ability to inhibit patients''IgE binding to these allergens (Figures 2A-C) .

abstract:
  In the last decade single domain antibodies (nanobodies, V(H)H) qualified through their unique characteristics have emerged as accepted and even advantageous alternative to conventional antibodies and have shown great potential as diagnostic and therapeutic tools. Currently nanobodies find their main medical application area in the fields of oncology and neurodegenerative diseases. According to late-breaking information, nanobodies specific for coronavirus spikes have been generated these days to test their suitability as useful therapeutics for future outbreaks. Their superior properties such as chemical stability, high affinity to a broad spectrum of epitopes, low immunogenicity, ease of their generation, selection and production proved nanobodies also to be remarkable to investigate their efficacy for passive treatment of type I allergy, an exaggerated immune reaction to foreign antigens with increasing global prevalence.


id: cord-282817-vtzpf2wr
title: A tale of two specificities: bispecific antibodies for therapeutic and diagnostic applications
author: Byrne, Hannah
date: 2013-10-02
txt: ./txt/cord-282817-vtzpf2wr.txt
cache: ./cache/cord-282817-vtzpf2wr.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/24094861/
doi: 10.1016/j.tibtech.2013.08.007
summary:
  Despite significant positive clinical results, especially in the case of hematological malignancies, adverse clinical outcomes and animal studies have highlighted underlying limitations of mAbs. Accordingly, many strategies have been developed in order to improve the specificity and control the functions of antibodies. The BiTE format potentially overcomes several limiting factors relating to the biological activity of tumor-directed bsAbs. BiTEs combine the minimal binding domains (Fv fragments) of two different mAbs fused together by a short flexible linker that allows free rotation of the two arms, and thus facilitates optimal antibody:antigen interaction [28] . bsAbs are attractive in such assays because they simplify the detection steps and are currently used for the development of simple, rapid, and highly sensitive immunoassays for the detection of bacterial and viral infectious diseases and in cancer diagnostics. CD40-targeted adenoviral gene transfer to dendritic cells through the use of a novel bispecific single-chain Fv antibody enhances cytotoxic T cell activation

abstract:
  Artificial manipulation of antibody genes has facilitated the production of several unique recombinant antibody formats, which have highly important therapeutic and biotechnological applications. Although bispecific antibodies (bsAbs) are not new, they are coming to the forefront as our knowledge of the potential efficacy of antibody-based therapeutics expands. The next generation of bsAbs is developing due to significant improvements in recombinant antibody technologies. This review focuses on recent advances with a particular focus on improvements in format and design that are contributing to the resurgence of bsAbs, and in particular, on innovative structures applicable to next generation point-of-care (POC) devices with applicability to low resource environments.


id: cord-283641-2u16otbf
title: Diagnostic Techniques: Serological and Molecular Approaches
author: Vainionpää, R.
date: 2015-03-06
txt: ./txt/cord-283641-2u16otbf.txt
cache: ./cache/cord-283641-2u16otbf.txt
extension: .txt
mime: text/plain
url: https://www.sciencedirect.com/science/article/pii/B9780128012383025587
doi: 10.1016/b978-0-12-801238-3.02558-7
summary:
  For diagnostic purposes the following approaches can be used: demonstration of presence of infectious virus or its structural components directly from a patient''s specimens or investigation of specific antibody response in serum specimens. Glossary EIA Enzyme immunoassays are methods used to estimate virus-specific IgG and IgM antibodies or virus antigens by enzyme-labeled conjugates. Nucleic acid testing has become the main approach for the demonstration of the presence of virus while cultivation is used by fewer specialized laboratories and antigen detection methods have moved to the point of care. Diagnostic applications of the measurement of the avidity of IgG antibodies against specific antigens have been developed to help distinguish serological responses due to acute infections from those of chronic or past infections. In immunofluorescence tests, cells from a clinical specimen are fixed on a glass slide and viral antigens present in the cells are detected by fluorescein-labeled virus-specific antibodies.

abstract:
  Virus laboratory diagnostics has an increasingly important role in modern patient care. Virological methods are needed to investigate the etiology of acute viral infection or the reactivation of a latent infection, as well as to follow virus load in antiviral treatments. Serological assays are also used for screening of blood products for the risk of certain chronic infections, evaluation of the immune status, and need for prophylactic treatments in connection with organ transplantations. For diagnostic purposes the following approaches can be used: demonstration of presence of infectious virus or its structural components directly from a patient's specimens or investigation of specific antibody response in serum specimens. Amplification techniques, most commonly polymerase chain reaction (PCR) is currently the workhorse of nucleic acid testing for the detection and quantitation of virus genomes. Virus isolation is used to demonstrate infectious virus in a patient's specimens, whereas virus antigens are investigated by antigen detection assays. Serological diagnosis is based on either the demonstration of the presence of virus-specific IgM antibodies or a significant increase in the levels and/or avidity of specific IgG antibodies. Immunoassays are the most commonly used serological assays. Point-of-care tests (POC tests), for antigens, antibodies, and also nucleic acids are also becoming more and more common in diagnostic use. In order to reach the best diagnostic efficiency for each patient it is important to select the most suitable method using the right sample collected at the right time.


id: cord-283826-lgyc3sro
title: Therapeutic Use of Immunoglobulins
author: Stiehm, E. Richard
date: 2010-11-05
txt: ./txt/cord-283826-lgyc3sro.txt
cache: ./cache/cord-283826-lgyc3sro.txt
extension: .txt
mime: text/plain
url: https://www.sciencedirect.com/science/article/pii/S006531011000006X
doi: 10.1016/j.yapd.2010.08.005
abstract: nan
summary:
  medical science and thereby placed in the hands of the physician a victorious weapon against illness and death.'' '' Since then antibodies in multiple forms (animal and human serums, immune globulins and monoclonal antibodies) have been developed, primarily for prevention of infectious diseases, and less commonly for their treatment. Thus regular use of IVIG in antibody-deficient patients in doses of 400 to 600 mg/kg every 3 to 4 weeks or an equivalent amount given subcutaneously decreases the frequency and severity of otitis and other respiratory tract infections [27, 28] . High-dose IVIG (sufficient to increase the serum IgG levels to 1000 mg/mL) has been used successfully in immunodeficient patients with enteroviral encephalomyelitis [80] [81] [82] [83] . Because IgG represents the major defense of humoral immunity against infection, these patients also require immunoglobulin replacement therapy. Individualizing the dose of intravenous immune serum globulin for therapy of patients with primary humoral immunodeficiency


id: cord-285760-y37ji92k
author: Connell, Anna R.
date: 2020-09-18
txt: ./txt/cord-285760-y37ji92k.txt
cache: ./cache/cord-285760-y37ji92k.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/33072071/
doi: 10.3389/fimmu.2020.02089
summary:
  Although a rise in IgG titer may also not occur in vaccinated individuals (87, 137) , numerous studies have documented a rapid, variable increase in mumps-specific IgG levels, with neutralization antibody concentrations present up to 10 months post-infection (130, 138, 139) . Potential waning immunity has been documented in the current mumps outbreaks seen in Europe and the USA, mostly affecting young adults within highly vaccinated populations attending tertiary education who have received two doses of the MMR vaccine in early childhood (40, 110, 126, 144, 145, (175) (176) (177) (178) (179) (180) (181) . Although MuV can be clinically asymptomatic in about 15-30% of those who become infected, the vaccine against mumps confers protection in a dose response manner; unvaccinated individuals saw an attack rate of Based on the reduction seen upon the introduction of a mumps vaccine, it has been proposed that MMR vaccination also prevents the transmission of the virus.

title:
  Mumps Outbreaks in Vaccinated Populations—Is It Time to Re-assess the Clinical Efficacy of Vaccines?

abstract:
  History illustrates the remarkable public health impact of mass vaccination, by dramatically improving life expectancy and reducing the burden of infectious diseases and co-morbidities worldwide. It has been perceived that if an individual adhered to the MMR vaccine schedule that immunity to mumps virus (MuV) would be lifelong. Recent mumps outbreaks in individuals who had received two doses of the Measles Mumps Rubella (MMR) vaccine has challenged the efficacy of the MMR vaccine. However, clinical symptoms, complications, viral shedding and transmission associated with mumps infection has been shown to be reduced in vaccinated individuals, demonstrating a benefit of this vaccine. Therefore, the question of what constitutes a good mumps vaccine and how its impact is assessed in this modern era remains to be addressed. Epidemiology of the individuals most affected by the outbreaks (predominantly young adults) and variance in the circulating MuV genotype have been well-described alluding to a collection of influences such as vaccine hesitancy, heterogeneous vaccine uptake, primary, and/or secondary vaccine failures. This review aims to discuss in detail the interplay of factors thought to be contributing to the current mumps outbreaks seen in highly vaccinated populations. In addition, how mumps diagnoses has progressed and impacted the understanding of mumps infection since a mumps vaccine was first developed, the limitations of current laboratory tests in confirming protection in vaccinated individuals and how vaccine effectiveness is quantified are also considered. By highlighting knowledge gaps within this area, this state-of-the-art review proposes a change of perspective regarding the impact of a vaccine in a highly vaccinated population from a clinical, diagnostic and public perspective, highlighting a need for a paradigm shift on what is considered vaccine immunity.


id: cord-290783-ipoelk4h
author: Crouch, C. F.
date: 1985-09-30
txt: ./txt/cord-290783-ipoelk4h.txt
cache: ./cache/cord-290783-ipoelk4h.txt
extension: .txt
mime: text/plain
url: https://api.elsevier.com/content/article/pii/S0264410X85900568
doi: 10.1016/s0264-410x(85)90056-8
summary:
  This article examines methods currently used to enhance the titre and duration of specific antibody in the mammary secretions of cows and pigs with particular reference to rotavirus and coronavirus infections. The situation in neonatal piglets is less clear, rotavirus infections are apparently common 6.t4-tt, w.hilst transmissible gastroenteritis virus (TGEV), the prototype enteric coronavirus in swine, is an example of a seasonal cold-weather disease, probably related to both the thermal sensitivity of the virus ~ and the effect of cold-stress on converting subclinical to clinical infections ~8. It is apparent that the enhancement of lactogenic immunity through the vaccination of the dam provides a suitable mechanism by which neonatal pigs and calves can be protected against rotavirus and coronavirus infections. Passive immunity in calf rotavirus infections: Maternal vaccination increases and prolongs immunoglobulin G 1 antibody secretion in milk Antibody responses in serum, colostrum and milk of swine after infection or vaccination with transmissible gastroenteritis virus

title:
  Vaccination against enteric rota and coronaviruses in cattle and pigs: Enhancement of lactogenic immunity

abstract:
  Passive immunity against enteric viral infections is dependent upon the continual presence in the gut lumen of a protective level of specific antibodies. This article examines methods currently used to enhance the titre and duration of specific antibody in the mammary secretions of cows and pigs with particular reference to rotavirus and coronavirus infections. In addition, some of the potential problems to be found in attempting to produce vaccines against these viral infections are outlined


id: cord-291626-lxa8pvt3
title: Monoclonal antibodies as anti-infective products: a promising future?
author: Pelfrene, E.
date: 2019-01-31
txt: ./txt/cord-291626-lxa8pvt3.txt
cache: ./cache/cord-291626-lxa8pvt3.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1016/j.cmi.2018.04.024
doi: 10.1016/j.cmi.2018.04.024
summary:
  Additionally, the FDA recently licensed ibalizumab as a rescue therapy in heavily treatmentexperienced adults with multidrug-resistant HIV-1 infection and also previously approved raxibacumab (in 2012) and obiltoxaximab (in 2016), both intended for treatment of inhalational anthrax (in combination with appropriate antibacterial medicines) and for prophylaxis when alternative therapies are not available or are not appropriate [5e7] . François et al., ''Safety and tolerability of a single administration of AR-301, a human monoclonal antibody, in patients with severe pneumonia caused by Staphylococcus aureus: first in man trial,'' abstract 1992, paper presented at European Congress of Clinical Microbiology and Infectious Diseases 2017) [34, 38] . Compassionate use Benefits seriously ill patients who cannot be treated satisfactorily or cannot enrol in ongoing clinical trials Pertains to unauthorized medicinal products for chronically, seriously debilitating or life-threatening diseases, with no satisfactory treatment authorized in EU; targeted at a group of patients rather than individual; or undergoing centralized MAA or clinical trials EMA, European Medicines Agency; FDA, US Food and Drug Administration; HTA, health technology assessment bodies; MAA, marketing authorization application; SA, scientific advice.

abstract:
  Abstract Background The paucity of licensed monoclonal antibodies (mAbs) in the infectious diseases arena strongly contrasts with the ready availability of these therapeutics for use in other conditions. Aims This narrative review aims to assess the potential of monoclonal antibody-based interventions for infectious diseases. Sources A review of the literature via the Medline database was performed and complemented by published official documents on licensed anti-infective mAbs. In addition, ongoing trials were identified through a search of the clinical trial registration platform ClinicalTrials.gov. Content We identified the few infections for which mAbs have been added to the therapeutic armamentarium and stressed their potential in representing a readily available protection tool against biothreats and newly emerging and reemerging infectious agents. In reviewing the historical context and main features of mAbs, we assert a potentially wider applicability and cite relevant examples of ongoing therapeutic developments. Factors hindering successful introduction of mAbs on a larger scale are outlined and thoughts are offered on how to possibly address some of these limitations. Implications mAbs may represent important tools in treating or preventing infections occurring with reasonably sufficient prevalence to justify demand and for which existing alternatives are not deemed fully adequate. Future initiatives need to address the prohibitive costs encountered in the development process. The feasibility of more large-scale administration of alternative modalities merits further exploration. In order to ensure optimal prospect of regulatory success, an early dialogue with competent authorities is encouraged.


id: cord-292874-6zjqflhz
title: Severe Acute Respiratory Syndrome (SARS): Development of Diagnostics and Antivirals
author: SØRENSEN, MORTEN DRÆBY
date: 2006-05-10
txt: ./txt/cord-292874-6zjqflhz.txt
cache: ./cache/cord-292874-6zjqflhz.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/16804033/
doi: 10.1196/annals.1354.072
summary:
  abstract: The previously unknown coronavirus that caused severe acute respiratory syndrome (SARS‐CoV) affected more than 8,000 persons worldwide and was responsible for more than 700 deaths during the first outbreak in 2002–2003. As part of the Sino‐European Project on SARS Diagnostics and Antivirals (SEPSDA), an immune phage‐display library is being created from convalescent patients in a phagemid system for the selection of single‐chain fragment variables (scFv) antibodies recognizing the SARS‐CoV. In February 2003, the new and previously unknown deadly coronavirus causing severe acute respiratory syndrome (SARS-CoV) was brought to the attention of the World Health Organization (WHO) by Dr. Carlo Urbani and his colleagues. Creation of immune phage-display libraries for immunized donors has shown a particular efficiency in selecting neutralizing antibodies (NABs) against different viruses, for example, rabies, 39 varicella-zoster, 40 hepatitis A 41 and E, 42 measles, 43 and respiratory syncytial virus.

abstract:
  abstract: The previously unknown coronavirus that caused severe acute respiratory syndrome (SARS‐CoV) affected more than 8,000 persons worldwide and was responsible for more than 700 deaths during the first outbreak in 2002–2003. For reasons unknown, the SARS virus is less severe and the clinical progression a great deal milder in children younger than 12 years of age. In contrast, the mortality rate can exceed 50% for persons at or above the age of 60. As part of the Sino‐European Project on SARS Diagnostics and Antivirals (SEPSDA), an immune phage‐display library is being created from convalescent patients in a phagemid system for the selection of single‐chain fragment variables (scFv) antibodies recognizing the SARS‐CoV.


id: cord-295033-5fd9bu60
author: Parma, Y.R.
date: 2011-09-15
txt: ./txt/cord-295033-5fd9bu60.txt
cache: ./cache/cord-295033-5fd9bu60.txt
extension: .txt
mime: text/plain
url: https://www.sciencedirect.com/science/article/pii/S0041010111002273
doi: 10.1016/j.toxicon.2011.07.009
summary:
  The data suggest that immunization of hens with Stx2B could be a strategy to obtain at low cost a relatively high concentration of anti-Stx2 egg yolk IgY, able to neutralize Stx2 lethal activity. The data suggest that immunization of hens with Stx2B could be a strategy to obtain at low cost a relatively high concentration of anti-Stx2 egg yolk IgY, able to neutralize Stx2 lethal activity. Specific anti-Stx2B polyclonal antibodies obtained from chicken egg yolk and rabbit sera recognized not only the denatured and native form of B subunit, used for immunization but the antibodies were also able to recognize the denatured and native wild type Stx2 holotoxin in western blot (Fig. 3) , indirect ELISA (Fig. 4) and sandwich ELISA (Fig. 5) . In the present report, specific egg yolk IgY antibodies with binding and neutralizing capabilities against the wild type Stx2 toxin were obtained after immunization of laying hens.

title:
  Antibodies anti-Shiga toxin 2 B subunit from chicken egg yolk: Isolation, purification and neutralization efficacy

abstract:
  Shiga toxins (Stx1 and Stx2) are the main virulence factors of enterohemorrhagic Escherichia coli (EHEC), a foodborne pathogen associated with diarrhea, hemorrhagic colitis and hemolytic uremic syndrome. The aim of this study was to evaluate the antibodies against Stx2 obtained from egg yolks of laying hens immunized with a recombinant Stx2B subunit. A high specific response in serum was observed 25 days after the first immunization and IgY antibodies were extracted from day 47th and purified from egg yolk. A concentration of 0.84 mg of total IgY/ml of egg yolk was obtained, of which 8% were antigen specific. The ability of anti-Stx2B IgY to recognize Stx2B and Stx2 either in solid-phase or in solution were evaluated and compared with anti-Stx2B rabbit antibodies by Western blotting and ELISA. The protective efficacy of IgY against Stx2 was determined by in vitro and in vivo experiments. The results show that IgY was able to recognize Stx2B and Stx2 in denatured conditions, attached to a solid-phase and free in solution. The anti-Stx2B IgY could effectively block the biological activity of Stx2 on Vero cells and protect mice from Stx2 challenge. The data suggest that immunization of hens with Stx2B could be a strategy to obtain at low cost a relatively high concentration of anti-Stx2 egg yolk IgY, able to neutralize Stx2 lethal activity. IgY technology could be an useful tool for research, diagnosis and therapy of EHEC infection.


id: cord-295099-ghc85pf5
title: Brief introduction of current technologies in isolation of broadly neutralizing HIV-1 antibodies
author: Sun, Zehua
date: 2018-01-02
url: https://doi.org/10.1016/j.virusres.2017.10.011
doi: 10.1016/j.virusres.2017.10.011
abstract:
  HIV/AIDS has become a worldwide pandemic. Before an effective HIV-1 vaccine eliciting broadly neutralizing monoclonal antibodies (bnmAbs) is fully developed, passive immunization for prevention and treatment of HIV-1 infection may alleviate the burden caused by the pandemic. Among HIV-1 infected individuals, about 20% of them generated cross-reactive neutralizing antibodies two to four years after infection, the details of which could provide knowledge for effective vaccine design. Recent progress in techniques for isolation of human broadly neutralizing antibodies has facilitated the study of passive immunization. The isolation and characterization of large panels of potent human broadly neutralizing antibodies has revealed new insights into the principles of antibody-mediated neutralization of HIV. In this paper, we review the current effective techniques in broadly neutralizing antibody isolation.


id: cord-296576-d23b9fjl
author: Bernard, Serge
date: 1990-01-31
txt: ./txt/cord-296576-d23b9fjl.txt
cache: ./cache/cord-296576-d23b9fjl.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/2156374/
doi: 10.1016/0165-2427(90)90076-5
summary:
  title: Lactogenic Immunity to Transmissible Gastroenteritis (TGE) of swine induced by the attenuated nouzilly strain of TGE virus: Passive protection of piglets and detection of serum and milk antibody classes by ELISA After natural infection or experimental oral infection of pregnant sows with a virulent strain of TGE virus, lactogenic immunity is highly protective for piglets, and neutralizing antibodies in milk are mainly associated with the IgA fraction (Bohl, 1981) . TABLE 3 Relationship between passive protection rate and titre of specific anti-TGE antibody classes ( IgG, IgA, IgM) in serum and milk, on the day and 10 days after challenge The most interesting result of the preliminary report about the immune response of sows vaccinated with N strain of TGE (Shira''i et al., 1988) was the absence of correlation between the passive protection rate of the litter and the neutralizing antibody titre in serum or milk of sows on the day of challenge.

title:
  Lactogenic Immunity to Transmissible Gastroenteritis (TGE) of swine induced by the attenuated nouzilly strain of TGE virus: Passive protection of piglets and detection of serum and milk antibody classes by ELISA

abstract:
  Abstract Piglets of eight sows vaccinated by different routes with the attenuated TGE mutant coronavirus, Nouzilly (N) strain, and piglets from two field seropositive sows were challenged with a virulent TGE strain. On the day of challenge and 10 days after challenge, milk and serum samples from sows were analysed for their level of neutralizing antibodies, total immunoglobulin classes and TGE antibody classes by an ELISA. No direct relationship was seen between the level of protection of the litters and the titres of the different antibody classes on the day of challenge. However, an inverse correlation was seen 10 days after challenge between protection and the level of TGE antibodies.


id: cord-296928-wu14k7u9
title: Greatest Hits—Innovative Technologies for High Throughput Identification of Bispecific Antibodies
author: Hofmann, Tim
date: 2020-09-08
txt: ./txt/cord-296928-wu14k7u9.txt
cache: ./cache/cord-296928-wu14k7u9.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.3390/ijms21186551
doi: 10.3390/ijms21186551
summary:
  In this review, we provide an overview of the most relevant methodologies for bispecific screening purposes—the DuoBody concept, paired light chain single cell production approaches, Sortase A and Transglutaminase, the SpyTag/SpyCatcher system, and inteins—and elaborate on the benefits as well as drawbacks of the different technologies. In order to overcome this bottleneck, technologies such as controlled Fab-arm exchange used for DuoBodies [22] , paired light chain single cell production approaches [23] , microbial transglutaminase [24] or Sortase A [25] mediated bioconjugation, the SpyTag/SpyCatcher system [26, 27] , or split inteins [28] were adapted to enable broad bispecific antibody screening ( Figure 1 ). In order to overcome this bottleneck, technologies such as controlled Fab-arm exchange used for DuoBodies [22] , paired light chain single cell production approaches [23] , microbial transglutaminase [24] or Sortase A [25] mediated bioconjugation, the SpyTag/SpyCatcher system [26, 27] , or split inteins [28] were adapted to enable broad bispecific antibody screening ( Figure 1 ).

abstract:
  Recent years have shown a tremendous increase and diversification in antibody-based therapeutics with advances in production techniques and formats. The plethora of currently investigated bi- to multi-specific antibody architectures can be harnessed to elicit a broad variety of specific modes of actions in oncology and immunology, spanning from enhanced selectivity to effector cell recruitment, all of which cannot be addressed by monospecific antibodies. Despite continuously growing efforts and methodologies, the identification of an optimal bispecific antibody as the best possible combination of two parental monospecific binders, however, remains challenging, due to tedious cloning and production, often resulting in undesired extended development times and increased expenses. Although automated high throughput screening approaches have matured for pharmaceutical small molecule development, it was only recently that protein bioconjugation technologies have been developed for the facile generation of bispecific antibodies in a ‘plug and play’ manner. In this review, we provide an overview of the most relevant methodologies for bispecific screening purposes—the DuoBody concept, paired light chain single cell production approaches, Sortase A and Transglutaminase, the SpyTag/SpyCatcher system, and inteins—and elaborate on the benefits as well as drawbacks of the different technologies.


id: cord-297684-9q3oopaz
author: Dobaño, Carlota
date: 2020-06-12
url: https://doi.org/10.1101/2020.06.11.147363
doi: 10.1101/2020.06.11.147363
title:
  Highly sensitive and specific multiplex antibody assays to quantify immunoglobulins M, A and G against SARS-CoV-2 antigens

abstract:
  Reliable serological tests are required to determine the prevalence of antibodies against SARS-CoV-2 antigens and to characterise immunity to the disease in order to address key knowledge gaps in the context of the COVID-19 pandemic. Quantitative suspension array technology (qSAT) assays based on the xMAP Luminex platform overcome the limitations of rapid diagnostic tests and ELISA with their higher precision, dynamic range, throughput, miniaturization, cost-efficacy and multiplexing capacity. We developed three qSAT assays to detect IgM, IgA and IgG to a panel of eight SARS-CoV-2 antigens including spike (S), nucleoprotein (N) and membrane (M) protein constructs. The assays were optimized to minimize processing time and maximize signal to noise ratio. We evaluated the performance of the assays using 128 plasmas obtained before the COVID-19 pandemic (negative controls) and 115 plasmas from individuals with SARS-CoV-2 diagnosis (positive controls), of whom 8 were asymptomatic, 58 had mild symptoms and 49 were hospitalized. Pre-existing IgG antibodies recognizing N, M and S2 proteins were detected in negative controls suggestive of cross-reactive to common cold coronaviruses. The best performing antibody isotype/antigen signatures had specificities of 100% and sensitivities of 94.94% at ≥14 days since the onset of symptoms and 96.08% at ≥21 days since the onset of symptoms, with AUC of 0.992 and 0.999, respectively. Combining multiple antibody markers as assessed by qSAT assays has the highest efficiency, breadth and versatility to accurately detect low-level antibody responses for obtaining reliable data on prevalence of exposure to novel pathogens in a population. Our assays will allow gaining insights into antibody correlates of immunity required for vaccine development to combat pandemics like the COVID-19.


id: cord-298910-2601n7a9
title: Generation and characterization of anti-α-enolase single-chain antibodies in chicken
author: Leu, Sy-Jye
date: 2010-10-15
txt: ./txt/cord-298910-2601n7a9.txt
cache: ./cache/cord-298910-2601n7a9.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/20655599/
doi: 10.1016/j.vetimm.2010.06.001
summary:
  The expressed heavy and light chain variable genes (VH and VL) were isolated from spleen B cells and amplified to construct phage antibody libraries containing scFv molecules. After four rounds of panning selection, the scFv antibodies of randomly chosen clones were expressed and their binding specificity to α-enolase protein was verified using competitive ELISA, flow cytometry and immunofluorescence staining. Accordingly, in the present study, we generated and characterized the anti-␣-enolase polyclonal IgY antibodies in chicken and monoclonal scFv antibodies by a phage display system using ELISA, Western blotting, flow cytometry and immunofluorescence staining. EnL2 and EnL5 scFv antibodies purified as a single band on SDS-PAGE (data not shown) were able to detect ␣-enolase protein in PE089 cells, and the binding signal is comparable to that of commercially available rabbit polyclonal antibodies specific for ␣-enolase as demonstrated in Fig. 7 .

abstract:
  It was previously reported that up-regulation of α-enolase protein was detected in 65% of patients with non-small cell lung cancers (NSCLC). Moreover, a high titer of anti-α-enolase antibodies was developed in a smaller proportion (7.4%) of these patients than in non-tumor-associated patients and healthy subjects. In the present study, we characterized polyclonal and single-chain variable fragment (scFv) anti-α-enolase antibodies from immunized chickens. The E. coli-derived recombinant α-enolase protein was purified to its high homogenicity as verified by SDS-PAGE. After the 4th immunization, a high titer of specific polyclonal anti-α-enolase antibodies was elicited in immunized chickens and specifically recognized the purified human α-enolase antigen as determined by Western blot and ELISA. The expressed heavy and light chain variable genes (VH and VL) were isolated from spleen B cells and amplified to construct phage antibody libraries containing scFv molecules. After four rounds of panning selection, the scFv antibodies of randomly chosen clones were expressed and their binding specificity to α-enolase protein was verified using competitive ELISA, flow cytometry and immunofluorescence staining. Nucleotide sequence analysis from 10 α-enolase binding clones showed that 3 (30%) clones used identical heavy and light genes for scFv antibody expression, as represented by EnL5. Notably, amino acid changes in complementarity-determining regions (CDRs) were more frequently observed than those in framework regions (FRs) in all clones, indicating a strong affinity selection through mutations. All together, it is believed that these polyclonal and scFv IgY antibodies may be helpful in the development of molecular diagnostic and therapeutic agents for lung cancers in the future.


id: cord-300701-vkzya7uq
author: Ijaz, M. K.
date: 1987-12-31
txt: ./txt/cord-300701-vkzya7uq.txt
cache: ./cache/cord-300701-vkzya7uq.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/2837143/
doi: 10.1016/s0166-3542(87)80006-2
summary:
  Summary The effect of different routes of immunization with either live or killed bovine rotavirus (BRV) on the production of lactogenic antibody response in mice was evaluated. Taking this into consideration, we have utilized the murine model to study the influence of different routes of immunization with either live or killed BRV on the rate of decline of antibody titers and different subtypes in the lacteal secretions of the da-m following parturition up to eleven days. Titers of anti-rotavirus antibodies in lacteal secretions, as determined by ELISA, also revealed a similar pattern as seen in the groups immunized with killed BRV. Although administration of live or killed BRV at mucosal sites (intestine and mammary regions) not only induced a significant elevation of IgA, IgM and IgG antibodies in lacteal secretions there was also a marked increase in serum anti-rotavirus antibodies as determined by ELISA.

title:
  Effect of different routes of immunization with bovine rotavirus on lactogenic antibody response in mice

abstract:
  Summary The effect of different routes of immunization with either live or killed bovine rotavirus (BRV) on the production of lactogenic antibody response in mice was evaluated. The routes of immunization were intramuscular (IM), oral (O) or intradermal in the mammary region (IMam). Following immunization, serum antibody responses were monitored by an enzyme linked immunosorbent assay (ELISA). Following whelping, the mice were allowed to stay with their mother until sacrificed on alternate days post-parturition from day 1–11. Milk from their stomach was collected for antibody titration by ELISA and virus neutralization test. Regardless of the routes of immunization, a rapid increase in serum anti-rotavirus antibody titers was observed for the first 5 wk after immunization followed by a gradual decline. After parturition, the mean antibody titer of lacteal secretions, as determined by ELISA, increased gradually for 7 days with the greatest increase on day 9, followed by a decrease in anti-rotavirus antibody. These titers also correlated with antibody titers in milk as measured by virus neutralization test. The best lactogenic antibody response was observed when IMam × IM × 2 route of immunization was used with live BRV as the antigen. Interestingly, immunization via the oral route with killed BRV also resulted in good antibody responses. In contrast, in the group where killed BRV was used, animals receiving 3× orally had the highest antibody titer. The distribution of different antibody subtypes in milk samples revealed IgG to be the predominant antibody followed by IgM and IgA. Irrespective of the route of administration, there was an increase in IgA on day 9 as compared to day 1 in most of the groups. The significant role played by mucosal immunity in passive protection and the possible ways to modulate subtype specific lactogenic immune response are discussed. Animals models; Lactogenic immunity; Rotaviruses


id: cord-302312-1pm17l5d
title: Therapeutic use of monoclonal antibodies: general aspects and challenges for drug delivery
author: Quinteros, Daniela A.
date: 2017-03-31
txt: ./txt/cord-302312-1pm17l5d.txt
cache: ./cache/cord-302312-1pm17l5d.txt
extension: .txt
mime: text/plain
url: https://api.elsevier.com/content/article/pii/B9780323461436000257
doi: 10.1016/b978-0-323-46143-6.00025-7
summary:
  In therapy, the development of targeted drug delivery represents, together with tissue repair, the main applications of antibody-conjugated nanoparticles. In addition to their own properties as pathogens or toxin neutralizers, as well as in the recruitment of immune elements (complement, improving phagocytosis, cytotoxicity antibody dependent by natural killer cells, etc.), they could carry several elements (toxins, drugs, fluorochroms, or even nanoparticles, etc.) and be used in several diagnostic procedures, or even in therapy to destroy a specific target. To treat HER2 positive breast cancer, anti-HER2 humanized Mabs are commonly used, although advances can be made in targeted cellular localization via conjugation strategy through a nano-particulate system focusing on surface modified ligand/receptor-mediated nano-therapy to target the tumor cell at the molecular level. Bio-conjugation strategies of therapeutic agents loaded nanoparticles with Mabs have exhibited a targeted drug delivery approach both in vitro and in vivo.

abstract:
  Monoclonal antibodies are routinely used in several fields but the great challenge has been their use as therapeutic agents for the treatment of diseases, such as breast cancer, leukemia, asthma, macular degeneration, arthritis, Crohn’s disease, and transplants, among others. Monoclonal antibodies are protein molecules made in the laboratory from hybridoma cells by recombinant DNA technology. Important advances have been made over the past decade to improve some critical points, such as safety and efficacy of the first generation of therapeutic antibodies. This type of molecules presents a significant challenge from the pharmaceutical point of view due to their characteristics, such as molecular size, stability, and solubility. In this chapter we have attempted to identify the major issues associated with therapeutic approaches, formulating drawbacks and delivering antibody drugs, particularly focused on the challenges and opportunities that these present for the future.


id: cord-302382-eifh95zm
title: Immunotherapeutic approaches to curtail COVID-19
author: Owji, Hajar
date: 2020-08-21
url: https://www.sciencedirect.com/science/article/pii/S1567576920324309?v=s5
doi: 10.1016/j.intimp.2020.106924
abstract:
  COVID-19, the disease induced by the recently emerged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has imposed an unpredictable burden on the world. Drug repurposing has been employed to rapidly find a cure; but despite great efforts, no drug or vaccine is presently available for treating or prevention of COVID-19. Apart from antivirals, immunotherapeutic strategies are suggested considering the role of the immune response as the host defense again the virus, and the fact that SARS-CoV-2 suppresses interferon induction as an immune evasion strategy. Active immunization through vaccines, interferon administration, passive immunotherapy by convalescent plasma or synthesized monoclonal and polyclonal antibodies, as well as immunomodulatory drugs, are different immunotherapeutic approaches that will be mentioned in this review. The focus would be on passive immunotherapeutic interventions. Interferons might be helpful in some stages. Vaccine development has been followed with unprecedented speed. Some of these vaccines have been advanced to human clinical trials. Convalescent plasma therapy is already practiced in many countries to help save the lives of severely ill patients. Different antibodies that target various steps of SARS-CoV-2 pathogenesis or the associated immune responses are also proposed. For treating the cytokine storm induced at a late stage of the disease in some patients, immune modulation through JAK inhibitors, corticosteroids, and some other cognate classes are evaluated. Given the changing pattern of cytokine induction and immune responses throughout the COVID-19 disease course, different adapted approaches are needed to help patients. Gaining more knowledge about the detailed pathogenesis of SARS-CoV-2, its interplay with the immune system, and viral-mediated responses are crucial to identify efficient preventive and therapeutic approaches. A systemic approach seems essential in this regard.


id: cord-302974-t1t89p8y
title: Antibody Testing For Covid-19: Can It Be Used As A Screening Tool In Areas With Low Prevalence?
author: Mathur, Gagan
date: 2020-05-15
txt: ./txt/cord-302974-t1t89p8y.txt
cache: ./cache/cord-302974-t1t89p8y.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1093/ajcp/aqaa082
doi: 10.1093/ajcp/aqaa082
abstract: nan
summary:
  Soon after detection of spread of SARS-CoV-2 in the United States (US), focus was on developing molecular nucleic acid detection tests (real-time reverse transcriptase polymerase chain reaction [RT-PCR]) for early diagnosis of infection in symptomatic patients, patients with known exposure, and patients who are at risk. The Trump administration and the media have been promoting antibody tests as a screening tool to allow individuals with positive results to get back to work and open our economy. The assumption is that the individuals with positive antibody tests have recovered from COVID-19 (symptomatic or asymptomatic) infection and have developed immunity to the virus. As of April 30, 2020, 10 antibody tests have been approved by the US Food and Drug Administration (FDA) under emergency use authorizations. Prematurely promoting antibody tests as a screening tool all over the US will give individuals, who test positive and are not actually immune to COVID-19, a false sense of protection.


id: cord-304214-66nxk4e8
title: Vectored immunoprophylaxis: an emerging adjunct to traditional vaccination
author: Sanders, John W.
date: 2017-02-10
txt: ./txt/cord-304214-66nxk4e8.txt
cache: ./cache/cord-304214-66nxk4e8.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/28883973/
doi: 10.1186/s40794-017-0046-0
summary:
  Rather than passively transfering pre-formed antibodies, VIP is a process in which genes encoding previously characterized neutralizing antibodies are vectored into non-hematopoietic cells which then secrete the monoclonal antibodes encoded by those genes [1] (See Fig. 1 .) This vectored delivery and production of specified antibodies allows for protection without generating a standard immune response and results in endogenous antibody production that has the potential to be sustained [9] . Saunders, et al., used an rAAV serotype 8 vector to produce a full length IgG of a simianized form of the broadly neutralizing antibody VRC07 in macaques which was protective against simian-human immunodeficiency virus (SHIV) infection 5.5 weeks after treatment [24] . Using HIV-1-infected humanized mice, Horwitz, et al., demonstrated that following initial treatment with anti-retroviral therapy (ART), a single injection of adeno-associated virus directing expression of broadly neutralizing antibody 10-1074, produced durable viremic control after the ART was stopped [26] .

abstract:
  The successful development of effective vaccines has been elusive for many of the world’s most important infectious diseases. Additionally, much of the population, such as the aged or immunocompromised, are unable to mount an effective immunologic response for existing vaccines. Vectored Immunoprophylaxis (VIP) is a novel approach designed to address these challenges. Rather than utilizing an antigen to trigger a response from the host’s immune system as is normally done with traditional vaccines, VIP genetically engineers the production of tailored antibodies from non-hematopoietic cells, bypassing the humoral immune system. Direct administration of genes encoding for neutralizing antibodies has proven to be effective in both preventing and treating several infectious diseases in animal models. While, a significant amount of work has focused on HIV, including an ongoing clinical trial, the approach has also been shown to be effective for malaria, dengue, hepatitis C, influenza, and more. In addition to presenting itself as a potentially efficient approach to solving long-standing vaccine challenges, the approach may be the best, if not only, method to vaccinate immunocompromised individuals. Many issues still need to be addressed, including which tissue(s) makes the most suitable platform, which vector(s) are most efficient at transducing the platform tissue used to secrete the antibodies, and what are the long-term effects of such a treatment. Here we provide a brief overview of this approach, and its potential application in treating some of the world’s most intractable infectious diseases.


id: cord-305039-grsv06j7
title: Clinical development of monoclonal antibody-based drugs in HIV and HCV diseases
author: Flego, Michela
date: 2013-01-04
txt: ./txt/cord-305039-grsv06j7.txt
cache: ./cache/cord-305039-grsv06j7.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/23289632/
doi: 10.1186/1741-7015-11-4
summary:
  As for HIV, mAbs directed against spike viral proteins, as well as against host receptors, may act at an early stage of infection by preventing the binding of the virus on the cell surface. In some chronic viral infections, virus-specific immune cells may persist in a ''non-functional'' state, because of an imbalance of immunoregulatory signals involving multiple inhibitory and activating receptors, triggered by soluble factors and/or cell surface ligands. Therapeutic approaches using specific mAbs to block host immunosuppressive molecules (antagonism) or to trigger activating receptors (agonism) may be a valid strategy to restore immune cell function and treat various chronic viral infections. In a proof-of-concept passive immunization trial with humans, it has been demonstrated that a cocktail of the three broadly neutralizing mAbs -2G12, 4E10 and 2F5was able to delay viral rebound in patients whose infections were fully suppressed by antiretroviral treatment before administration of the antibodies [76] .

abstract:
  Today there are many licensed antiviral drugs, but the emergence of drug resistant strains sometimes invalidates the effects of the current therapies used in the treatment of infectious diseases. Compared to conventional antiviral drugs, monoclonal antibodies (mAbs) used as pharmacological molecules have particular physical characteristics and modes of action, and, therefore, they should be considered as a distinct therapeutic class. Despite being historically validated, antibodies may represent a novel tool for combatting infectious diseases. The current high cost of mAbs' production, storage and administration (by injection only) and the consequent obstacles to development are outweighed by mAbs' clinical advantages. These are related to a low toxicity combined with high specificity and versatility, which allows a specific antibody to mediate various biological effects, ranging from the virus neutralization mechanisms to the modulation of immune responses. This review briefly summarizes the recent technological advances in the field of immunoglobulin research, and the current status of mAb-based drugs in clinical trials for HIV and HCV diseases. For each clinical trial the available data are reported and the emerging conceptual problems of the employed mAbs are highlighted. This overview helps to give a clear picture of the efficacy and challenges of the mAbs in the field of these two infectious diseases which have such a global impact.


id: cord-305893-2vcy0f6i
author: Bagheri, Vahid
date: 2017-01-15
txt: ./txt/cord-305893-2vcy0f6i.txt
cache: ./cache/cord-305893-2vcy0f6i.txt
extension: .txt
mime: text/plain
url: https://www.sciencedirect.com/science/article/pii/S0024320516306713
doi: 10.1016/j.lfs.2016.11.018
summary:
  title: Neutralizing human recombinant antibodies against herpes simplex virus type 1 glycoproteins B from a phage-displayed scFv antibody library Our present study focused on the selection of neutralizing single-chain Fv (scFv) antibodies of a phage-displayed nonimmune human scFv antibody library against gB of HSV-1. described a neutralizing scFv-phage antibody against glycoprotein D of HSV-1 with neutralizing effect of 76%, which was capable of neutralizing HSV-1 and inhibiting virus entry to host cell [21] . Here, we selected two neutralizing anti-gB scFv antibodies to inhibit cytopathic effects in Vero cells infected with HSV-1. Neutralizing human single-chain antibodies against herpes simplex virus type 1 glycoprotein D from a phage display library Directed selection of recombinant human monoclonal antibodies to herpes simplex virus glycoproteins from phage display libraries

title:
  Neutralizing human recombinant antibodies against herpes simplex virus type 1 glycoproteins B from a phage-displayed scFv antibody library

abstract:
  Abstract The HSV-1 envelope glycoprotein B (gB) plays a critical role in virus entry into host cells. Neutralizing antibodies can therefore potentially prevent virus entry into target cells and cell-to-cell spread of infection. Our present study focused on the selection of neutralizing single-chain Fv (scFv) antibodies of a phage-displayed nonimmune human scFv antibody library against gB of HSV-1. To enrich specific scFvs, two phage antibodies were isolated against amino acid residues 31–43 derived from the N-terminal part of gB using panning technique. Two scFvs, scFv-gB1 and scFv-gB2, with frequencies of 45% and 20% were obtained from scFv clones after performing PCR and MvaI fingerprinting. In phage ELISA analysis, both gB1 and gB2 scFvs demonstrated high reactivity with the gB peptide. In the neutralization assay, scFv-gB1 and scFv-gB2 represented neutralizing effects of 55% and 59%, respectively. Upon further enhancement of the neutralizing effects of these antibodies, they can be considered as new potential alternatives in the treatment and prophylaxis of HSV-1 infections.


id: cord-307320-fxs31d66
title: Monoclonal Antibodies and Antibody Like Fragments Derived from Immunised Phage Display Libraries
author: Ubah, Obinna
date: 2018-03-17
txt: ./txt/cord-307320-fxs31d66.txt
cache: ./cache/cord-307320-fxs31d66.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/29549637/
doi: 10.1007/978-3-319-72077-7_6
summary:
  However, by combining the power of immunisation with phage display, several high affinity monoclonal antibodies against "difficult" antigenic targets have been isolated from relative small antibody libraries and where traditional approaches have failed [33, 98] . The above study demonstrates the power of animal immunisation and phage display based selection strategies to isolate high affinity monoclonal antibodies towards non-antigenic targets which inherently lack properties like aromaticity and charge. Spleen samples from mice immunised with gamma inactivated Brucella melitensis strain 16 M bacteria was used to construct a phage display library and isolate monoclonal antibody fragments that specifically recognise Brucella species. Similarly high affinity neutralising antibody fragments against the protective antigen (PA) of anthrax toxin was isolated from a Macaca immunised phage display library. Lymphocytes from the bone marrow cells of two chimpanzees immunised with anthrax toxin PA, LF and Edema factor (EF) were used to construct scFv phage display libraries and neutralising antibodies were isolated against PA and LF proteins.

abstract:
  Morbidity and mortality associated with infectious diseases are always on the rise, especially in poorer countries and in the aging population. The inevitable, but unpredictable emergence of new infectious diseases has become a global threat. HIV/AIDS, severe acute respiratory syndrome (SARS), and the more recent H1N1 influenza are only a few of the numerous examples of emerging infectious diseases in the modern era. However despite advances in diagnostics, therapeutics and vaccines, there is need for more specific, efficacious, cost-effective and less toxic treatment and preventive drugs. In this chapter, we discuss a powerful combinatorial technology in association with animal immunisation that is capable of generating biologic drugs with high affinity, efficacy and limited off-site toxicity, and diagnostic tools with great precision. Although time consuming, immunisation still remains the preferred route for the isolation of high-affinity antibodies and antibody-like fragments. Phage display is a molecular diversity technology that allows the presentation of large peptide and protein libraries on the surface of filamentous phage. The selection of binding fragments from phage display libraries has proven significant for routine isolation of invaluable peptides, antibodies, and antibody-like domains for diagnostic and therapeutic applications. Here we highlight the many benefits of combining immunisation with phage display in combating infectious diseases, and how our knowledge of antibody engineering has played a crucial role in fully exploiting these platforms in generating therapeutic and diagnostic biologics towards antigenic targets of infectious organisms.


id: cord-309067-aemjbkfj
title: Methodology in diagnostic virology
author: Kennedy, Melissa
date: 2005-03-01
url: https://api.elsevier.com/content/article/pii/S1094919404000702
doi: 10.1016/j.cvex.2004.09.009
abstract:
  Selection of proper assays and appropriate interpretation of results can be a challenge to the veterinary clinician. Assays vary in methodology, sensitivity, and specificity. These assays can be invaluable in attaining the correct diagnosis, but a clear understanding of the assay and the results is essential. To this end, communication with the laboratory personnel is crucial. Optimal sample selection, shipping recommendations, assay selection, and interpretation should be discussed with the laboratory staff.


id: cord-311811-nrodyagi
title: The use of host factors in microbial forensics
author: Schutzer, Steven E.
date: 2019-12-06
url: https://www.sciencedirect.com/science/article/pii/B9780128153796000143
doi: 10.1016/b978-0-12-815379-6.00014-3
abstract:
  Advances have been made in the forensic analysis of microbes and toxins. An underdeveloped and underutilized area in microbial forensics is how the host interacts with microorganisms in a way that provides unique signatures for forensic use. For forensic purposes, an immediate goal is to distinguish a potential victim and innocent person from a perpetrator, and to distinguish between a naturally acquired or intentional infection. Principal methods that are sufficiently developed are characterization of the humoral immune response to microbial antigens including vaccine-induced immunity and detection of antibiotics that may be present in a possible perpetrator. This chapter presents central elements of the host response in a simplified fashion and describes a representative example, which, in the appropriate context, has a high potential of providing evidence that may aid an investigation to distinguish a perpetrator from a victim. This chapter also presents information about the immune system so that the interested reader can have a fuller understanding of the immune response in general.


id: cord-312787-j7ye7ed5
author: Loemba, H. D.
date: 1996
txt: ./txt/cord-312787-j7ye7ed5.txt
cache: ./cache/cord-312787-j7ye7ed5.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/8645111/
doi: 10.1007/bf01718333
summary:
  coli-expressed ORFs 5 to 7 gene products, suggested that antibodies directed against the envelope E protein appear by day 7 p.i., whereas antibodies directed against the nucleocapsid N and membrane M proteins can only be detected by the end of the second week p.i. No correlation could be demonstrated between VN and IIF antibody titers, viremia, and viral protein specificities of circulating antibodies at various times p.i. Summary. coli-expressed ORFs 5 to 7 gene products, suggested that antibodies directed against the envelope E protein appear by day 7 p.i., whereas antibodies directed against the nucleocapsid N and membrane M proteins can only be detected by the end of the second week p.i. No correlation could be demonstrated between VN and IIF antibody titers, viremia, and viral protein specificities of circulating antibodies at various times p.i. The porcine reproductive and respiratory syndrome virus (PRRSV) is an enveloped RNA virus which has been found to be responsible for reproductive failure in sows of any parities (late-term abortions, increased numbers of stillborn, mummified and weakborn pigs) and respiratory problems affecting pigs of all ages [8, 20] .

title:
  Kinetics of humoral immune response to the major structural proteins of the porcine reproductive and respiratory syndrome virus

abstract:
  The kinetics of appearance of antibodies directed to the major structural proteins N, M and E of porcine reproductive and respiratory syndrome virus (PRRSV) was followed in pigs naturally- and experimentally-exposed to the virus. Specific IgM antibody titers were first detected by indirect immunofluorescence (IIF) at the end of the first week of PRRSV infection, peaked by day 14 to 21 post-inoculation (p.i.), then rapidly decreased to undetectable levels by day 35 to 42 p.i. On the other hand, specific IgG antibody titers peaked by day 21 to 28 p.i. and remained unchanged to the end of the 6- or 9-week observation period; in addition, a persistent viremia was observed. Virus neutralizing (VN) antibody titers >8 were not detected until 3 to 4 weeks p.i. Taken together, the results obtained by Western blotting analyses using purified virus andE. coli-expressed ORFs 5 to 7 gene products, suggested that antibodies directed against the envelope E protein appear by day 7 p.i., whereas antibodies directed against the nucleocapsid N and membrane M proteins can only be detected by the end of the second week p.i. No correlation could be demonstrated between VN and IIF antibody titers, viremia, and viral protein specificities of circulating antibodies at various times p.i.


id: cord-313312-h607itv2
title: The Effects of Pre-Existing Antibodies on Live-Attenuated Viral Vaccines
author: Mok, Darren Z. L.
date: 2020-05-08
txt: ./txt/cord-313312-h607itv2.txt
cache: ./cache/cord-313312-h607itv2.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/32397218/
doi: 10.3390/v12050520
summary:
  Pre-existing antibodies, derived from either from maternal–fetal transmission, or by previous infection or vaccination, have been demonstrated to interfere with vaccine immunogenicity of measles, adenovirus, and influenza LAVs. Immune interference of LAVs can be caused by the formation of virus–antibody complexes that neutralize virus infection in antigen-presenting cells, or by the cross-linking of the B-cell receptor with the inhibitory receptor, FcγRIIB. The clinical trial finding that subjects with a limited range of cross-reactive antibodies from a prior Japanese Encephalitis vaccine were able to enhance yellow fever vaccination, by prolonging vaccine viremia duration that leads to higher antibody titers, thus hints at the possibility that whether pre-existing antibodies inhibit or augment flavivirus infection will depend on both antibody titers and the type/specificity of antibodies produced [85] . By contrast, at sub-neutralizing titers, pre-existing antibodies can enable viruses to better infect cells and increase innate immune responses that augment LAV immunogenicity. By contrast, at sub-neutralizing titers, pre-existing antibodies can enable viruses to better infect cells and increase innate immune responses that augment LAV immunogenicity.

abstract:
  Live-attenuated vaccines (LAVs) have achieved remarkable successes in controlling virus spread, as well as for other applications such as cancer immunotherapy. However, with rapid increases in international travel, globalization, geographic spread of viral vectors, and widespread use of vaccines, there is an increasing need to consider how pre-exposure to viruses which share similar antigenic regions can impact vaccine efficacy. Pre-existing antibodies, derived from either from maternal–fetal transmission, or by previous infection or vaccination, have been demonstrated to interfere with vaccine immunogenicity of measles, adenovirus, and influenza LAVs. Immune interference of LAVs can be caused by the formation of virus–antibody complexes that neutralize virus infection in antigen-presenting cells, or by the cross-linking of the B-cell receptor with the inhibitory receptor, FcγRIIB. On the other hand, pre-existing antibodies can augment flaviviral LAV efficacy such as that of dengue and yellow fever virus, especially when pre-existing antibodies are present at sub-neutralizing levels. The increased vaccine immunogenicity can be facilitated by antibody-dependent enhancement of virus infection, enhancing virus uptake in antigen-presenting cells, and robust induction of innate immune responses that promote vaccine immunogenicity. This review examines the literature on this topic and examines the circumstances where pre-existing antibodies can inhibit or enhance LAV efficacy. A better knowledge of the underlying mechanisms involved could allow us to better manage immunization in seropositive individuals and even identify possibilities that could allow us to exploit pre-existing antibodies to boost vaccine-induced responses for improved vaccine efficacy.


id: cord-316287-4i1grvlr
author: Yim, Sung Sun
date: 2014-10-10
txt: ./txt/cord-316287-4i1grvlr.txt
cache: ./cache/cord-316287-4i1grvlr.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1371/journal.pone.0108225
doi: 10.1371/journal.pone.0108225
summary:
  During the cultivation for regeneration of sorted cells, differential growth rates among various clones (particularly non-specific clones) due to unregulated protein expression and differing cell viability can decrease the library screening efficiency, resulting in more rounds of sorting (longer duration) to isolate the potential antibody candidate [12] . The whole FACS screening rounds of the synthetic human antibody library against each viral antigen could be done in one day, and these results show that repeated FACS screening without regeneration of the sorted cells can be a rapid and efficient method to isolate potential antibody candidates in case of urgent requirements. For the FACS screening of a human synthetic antibody (scFv) library, three fluorescent antigen probes were chemically synthesized: (i) FITC-CRDNWHGSNRPW as an N1 epitope of H1N1 influenza virus [13] ; (ii) FITC-NSTTFHQALLDPRVRGLYF-PAGG as a PreS2 epitope of HBV [14] ; and (iii) FITC-PVTNVRGDLQVLAQK as a VP1 epitope of FMDV [15] .

title:
  Rapid Isolation of Antibody from a Synthetic Human Antibody Library by Repeated Fluorescence-Activated Cell Sorting (FACS)

abstract:
  Antibodies and their derivatives are the most important agents in therapeutics and diagnostics. Even after the significant progress in the technology for antibody screening from huge libraries, it takes a long time to isolate an antibody, which prevents a prompt action against the spread of a disease. Here, we report a new strategy for isolating desired antibodies from a combinatorial library in one day by repeated fluorescence-activated cell sorting (FACS). First, we constructed a library of synthetic human antibody in which single-chain variable fragment (scFv) was expressed in the periplasm of Escherichia coli. After labeling the cells with fluorescent antigen probes, the highly fluorescent cells were sorted by using a high-speed cell sorter, and these cells were reused without regeneration in the next round of sorting. After repeating this sorting, the positive clones were completely enriched in several hours. Thus, we screened the library against three viral antigens, including the H1N1 influenza virus, Hepatitis B virus, and Foot-and-mouth disease virus. Finally, the potential antibody candidates, which show K(D) values between 10 and 100 nM against the target antigens, could be successfully isolated even though the library was relatively small (∼10(6)). These results show that repeated FACS screening without regeneration of the sorted cells can be a powerful method when a rapid response to a spreading disease is required.


id: cord-317501-yblzopc3
author: Kuhn, Philipp
date: 2016-06-21
txt: ./txt/cord-317501-yblzopc3.txt
cache: ./cache/cord-317501-yblzopc3.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/27198131/
doi: 10.1002/prca.201600002
summary:
  Panning against peptides, recombinant viral proteins, or complete virus particles has led to the identification of antibodies directed against human pathogenic viruses such as Sin nombre virus [100] , Dengue virus [101, 102] , Influenza virus [103, 104] , VEEV [105] , Norovirus [106] , SARS coronavirus [107] , or Hepatitis C [108] from naïve antibody gene libraries. A naïve human Fab-phage library was screened for NS5-specific antibody fragments using various NS5 variants from Dengue Virus serotypes 1-4 as antigens for panning and characterization [128] . [180] reported the isolation of a human monoclonal antibody against the Block 2 region of Plasmodium falciparum merozoite surface protein-1 (PfMSP-1) by phage display from a malaria patient derived scFv library. In this context, the antibody phage display offers a powerful tool for antibody selection and allows the isolation of neutralizing antibodies against complete active toxins or special domains by using different human naïve antibody libraries with high diversity [185] [186] [187] . Single chain variable fragment antibodies against Shiga toxins isolated from a human antibody phage display library

title:
  Recombinant antibodies for diagnostics and therapy against pathogens and toxins generated by phage display

abstract:
  Antibodies are valuable molecules for the diagnostic and treatment of diseases caused by pathogens and toxins. Traditionally, these antibodies are generated by hybridoma technology. An alternative to hybridoma technology is the use of antibody phage display to generate recombinant antibodies. This in vitro technology circumvents the limitations of the immune system and allows—in theory—the generation of antibodies against all conceivable molecules. Phage display technology enables obtaining human antibodies from naïve antibody gene libraries when either patients are not available or immunization is not ethically feasible. On the other hand, if patients or immunized/infected animals are available, it is common to construct immune phage display libraries to select in vivo affinity‐matured antibodies. Because the phage packaged DNA sequence encoding the antibodies is directly available, the antibodies can be smoothly engineered according to the requirements of the final application. In this review, an overview of phage display derived recombinant antibodies against bacterial, viral, and eukaryotic pathogens as well as toxins for diagnostics and therapy is given.


id: cord-319746-6bccxgbd
author: Saxena, Latika
date: 2015-12-31
txt: ./txt/cord-319746-6bccxgbd.txt
cache: ./cache/cord-319746-6bccxgbd.txt
extension: .txt
mime: text/plain
url: https://api.elsevier.com/content/article/pii/S1877282X15000107
doi: 10.1016/j.provac.2015.05.009
summary:
  title: Production and Characterization of Human Monoclonal Antibodies from the Cells of A(H1N1)pdm2009 Influenza Virus Infected Indian Donors Abstract Analysis of human monoclonal antibodies (mAbs) developed from influenza infected donors have enormously contributed to the identification of neutralization sensitive epitopes of influenza virus. In this study, we generated strongly neutralizing novel human monoclonal antibodies that were selected from the immune repertoire of influenza infected seropositive patients. Monoclonal antibody 2D8 showed the maximum binding in the in vitro assays and neutralized the human isolate of the pandemic strain as well as the reference strain at lowest concentrations when compared to the 2F12 antibody. The antibodies however, showed comparative neutralization and HAI activity between the laboratory isolates of the pandemic virus and the reference strain A/Cal/07/2009(H1N1). To, the best of our knowledge, these antibodies are the first fully human monoclonal antibodies generated from the immune repertoire of Indian patients infected with A(H1N1)pdm09 virus.

title:
  Production and Characterization of Human Monoclonal Antibodies from the Cells of A(H1N1)pdm2009 Influenza Virus Infected Indian Donors

abstract:
  Abstract Analysis of human monoclonal antibodies (mAbs) developed from influenza infected donors have enormously contributed to the identification of neutralization sensitive epitopes of influenza virus. The HA protein is a crucial target of neutralizing antibodies and at monoclonal level only Abs binding to HA have been able to neutralize the virus. In this study, eight A (H1N1)pdm 2009 seropositive patients within the age range of 20-50 years (median=36 years) were recruited. Two anti-HA mAbs secreting stable clones, 2D8 and 2F12 were established under optimized conditions from the peripheral blood mononuclear cells (PBMCs) of the volunteers. These antibodies efficiently neutralized the homologous laboratory isolated strain of the pandemic virus as well as the reference strain. Our study suggests that the anti-HA antibodies derived from infected Indian patients display neutralization potential against the A(H1N1)pdm 2009 virus. This is the first ever study of generation of mAbs against the pandemic influenza virus involving the immune repertoire if Indian patients. Molecular characterization of the target regions will help in identifying potential immunogens in the Indian pandemic isolates and confer protective immunity against this virus.


id: cord-319884-d8n0aokl
title: Protein Microarrays and Biomarkers of Infectious Disease
author: Natesan, Mohan
date: 2010-12-16
txt: ./txt/cord-319884-d8n0aokl.txt
cache: ./cache/cord-319884-d8n0aokl.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.3390/ijms11125165
doi: 10.3390/ijms11125165
summary:
  Fluorescencebased detection of protein interactions is similar to gene array methods, and data analysis often employs approaches previously developed for genome and transcription studies. A standard assay for measuring antibody interactions with proteins of the vaccinia proteome microarray was first developed with a pool of therapeutic human sera collected from vaccinia-immune individuals (VIg) and this data was compared to results obtained from individuals vaccinated against smallpox using Dryvax. Results from this study suggested that antibodies from vaccination recognized a small number of proteins shared with pathogenic viral strains, while recovery from infection also involved humoral immunity to antigens uniquely recognized within the monkeypox virus proteome (unpublished data). For example, a protein array produced from the outer membrane proteins of Pseudomonas aeruginosa was constructed [38] to study the immune response in patients, and several antibody-binding antigens were identified by this group as potential diagnostic markers.

abstract:
  Protein microarrays are powerful tools that are widely used in systems biology research. For infectious diseases, proteome microarrays assembled from proteins of pathogens will play an increasingly important role in discovery of diagnostic markers, vaccines, and therapeutics. Distinct formats of protein microarrays have been developed for different applications, including abundance-based and function-based methods. Depending on the application, design issues should be considered, such as the need for multiplexing and label or label free detection methods. New developments, challenges, and future demands in infectious disease research will impact the application of protein microarrays for discovery and validation of biomarkers.


id: cord-321369-xzu2faol
title: Extremely potent human monoclonal antibodies from convalescent Covid-19 patients
author: Andreano, Emanuele
date: 2020-10-07
txt: ./txt/cord-321369-xzu2faol.txt
cache: ./cache/cord-321369-xzu2faol.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1101/2020.10.07.328302
doi: 10.1101/2020.10.07.328302
summary:
  By single cell sorting 4277 SARS-CoV-2 spike protein specific memory B cells from 14 Covid-19 survivors, 453 neutralizing antibodies were identified and 220 of them were expressed as IgG. The three most potent monoclonal antibodies identified were able to neutralize the wild type and D614G mutant viruses with less than 10 ng/mL and are good candidates for the development of prophylactic and therapeutic tools against SARS-CoV-2. As for the authentic virus neutralization assay, supernatants containing naturally produced IgG or IgA were tested for their ability to protect the layer of Vero E6 cells from the cytopathic effect triggered by SARS-CoV-2 infection (Fig. S2) . This work describes a systematic screening of memory B cells from convalescent people to identify extremely potent human monoclonal antibodies against the spike protein of the SARS-CoV-2 virus, to be used for prevention and therapy of Covid-19.

abstract:
  Human monoclonal antibodies are safe, preventive and therapeutic tools, that can be rapidly developed to help restore the massive health and economic disruption caused by the Covid-19 pandemic. By single cell sorting 4277 SARS-CoV-2 spike protein specific memory B cells from 14 Covid-19 survivors, 453 neutralizing antibodies were identified and 220 of them were expressed as IgG. Up to 65,9% of monoclonals neutralized the wild type virus at a concentration of >500 ng/mL, 23,6% neutralized the virus in the range of 100 - 500 ng/mL and 9,1% had a neutralization potency in the range of 10 - 100 ng/mL. Only 1,4% neutralized the authentic virus with a potency of 1-10 ng/mL. We found that the most potent neutralizing antibodies are extremely rare and recognize the RBD, followed in potency by antibodies that recognize the S1 domain, the S-protein trimeric structure and the S2 subunit. The three most potent monoclonal antibodies identified were able to neutralize the wild type and D614G mutant viruses with less than 10 ng/mL and are good candidates for the development of prophylactic and therapeutic tools against SARS-CoV-2. One Sentence Summary Extremely potent neutralizing human monoclonal antibodies isolated from Covid-19 convalescent patients for prophylactic and therapeutic interventions.


id: cord-321901-zpi7uis1
author: Roberts, Anjeanette
date: 2006-11-30
txt: ./txt/cord-321901-zpi7uis1.txt
cache: ./cache/cord-321901-zpi7uis1.txt
extension: .txt
mime: text/plain
url: https://www.sciencedirect.com/science/article/pii/S0264410X06008231
doi: 10.1016/j.vaccine.2006.07.009
summary:
  Scientists at the WHO Technical Meeting on Animal Models and Antibody Assays for Evaluating Candidate SARS Vaccines held on 25-26 August 2005 in South Mimms, UK, discussed many aspects of research pertaining to the use of animal models in vaccine development including available animal models, suitability of the various models, correlates of protection, critical components of potential vaccines, and the potential for disease enhancement in vaccinated animals following exposure to SARS-CoV. It may actually be worthwhile to enhance the virulence of a SARS-CoV isolate by serial passages in an animal model to produce a challenge virus stock for vaccine studies that would elicit more reproducible disease in the animals. Although none of the studies to date have shown enhanced respiratory disease following SARS-CoV challenge in previously immunized animals, further studies in this area are warranted in view of some of the available in vitro data. Development and characterization of a severe acute respiratory syndrome-associated coronavirus-neutralizing human monoclonal antibody that provides effective immunoprophylaxis in mice

title:
  Animal models and antibody assays for evaluating candidate SARS vaccines: Summary of a technical meeting 25–26 August 2005, London, UK

abstract:
  Abstract Severe acute respiratory syndrome (SARS) emerged in the Guangdong province of China in late 2002 and spread to 29 countries. By the end of the outbreak in July 2003, the CDC and WHO reported 8437 cases with a 9.6% case fatality rate. The disease was caused by a previously unrecognized coronavirus, SARS-CoV. Drawing on experience with animal coronavirus vaccines, several vaccine candidates have been developed and evaluated in pre-clinical trials. Available data suggest that vaccines should be based on the the 180kDa viral spike protein, S, the only significant neutralization antigen capable of inducing protective immune responses in animals. In the absence of clinical cases of SARS, candidate vaccines should be evaluated for efficacy in animal models, and although it is uncertain whether the United States Food and Drug Administration's “animal rule” would apply to licensure of a SARS vaccine, it is important to develop standardized animal models and immunological assays in preparation for this eventuality. This report summarizes the recommendations from a WHO Technical Meeting on Animal Models and Antibody Assays for Evaluating Candidate SARS Vaccines held on 25–26 August 2005 in South Mimms, UK, provides guidance on the use of animal models, and outlines the steps to develop standard reagents and assays for immunological evaluation of candidate SARS vaccines.


id: cord-324316-ulb8d5fe
title: Antibodies as Currency: COVID-19’s Golden Passport
author: Bramstedt, Katrina A.
date: 2020-08-25
txt: ./txt/cord-324316-ulb8d5fe.txt
cache: ./cache/cord-324316-ulb8d5fe.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1007/s11673-020-09996-5
doi: 10.1007/s11673-020-09996-5
summary:
  Due to COVID-19, the fragile economy, travel restrictions, and generalized anxieties, the concept of antibodies as a "declaration of immunity" or "passport" is sweeping the world. Numerous scientific and ethical issues confound the concept of an antibody passport; nonetheless, antibodies can be seen as a potential currency to allow movement of people and resuscitation of global economics. In this way, antibodies for SARS-CoV-2 (severe acute respiratory syndrome coronavirus type 2-the COVID-19 coronavirus) are potentially the new golden passport, but the concept is a moving target with clinical unknowns, as well as legal and ethical complexity (Phelan 2020; Persad and Emanuel 2020) . With the COVID-19 pandemic causing a fragile worldwide economy and millions of people unemployed (Congressional Research Service 2020), there is a risk of antibody certificates being viewed as the "golden passport" to return to work and travel. Show me your passport: Ethical concerns about Covid-19 antibody testing as key to reopening public life

abstract:
  Due to COVID-19, the fragile economy, travel restrictions, and generalized anxieties, the concept of antibodies as a “declaration of immunity” or “passport” is sweeping the world. Numerous scientific and ethical issues confound the concept of an antibody passport; nonetheless, antibodies can be seen as a potential currency to allow movement of people and resuscitation of global economics. Just as financial currency can be forged, so too is the potential for fraudulent antibody passports. This paper explores matters of science, ethics, and identity theft, as well as the problems of bias and discrimination that could promulgate a world of pandemic “golden passports.”


id: cord-326673-p8qbxi57
author: Kitching, R. P.
date: 1995-12-31
txt: ./txt/cord-326673-p8qbxi57.txt
cache: ./cache/cord-326673-p8qbxi57.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/7552194/
doi: 10.1016/s0007-1935(95)80127-8
summary:
  This maternally-derived antibody (MDA) provides immediate protection against infection with FMD virus, but also interferes with the development of active immunity following vaccination. However, this maternally derived antibody (MDA) is equally effective in preventing the response to active vaccination in the young animal as it is in providing protection against disease. In the case of FMD vaccination in pigs, Francis and Black (1986) concluded that the complete immunological unresponsiveness seen in the first 2 weeks of life was due to immaturity of the immune system and antigen blockade by high titre MDA, and as this titre declined an active suppression of T and/or B cells occurred to variable degrees. Francis and Black (1984) found no evidence in the pig that vaccination in the presence of MDA depressed the specific antibody to FMD virus. The effect of maternally derived antibodies on the response of calves to vaccination against foot-and-mouth disease

title:
  The interference by maternally-derived antibody with active immunization of farm animals against foot-and-mouth disease

abstract:
  Summary Foot-and-mouth disease (FMD) is a highly contagious disease affectingruminants and pigs. In countries in which control of FMD relies predominantly on vaccination, young stock ingest specific anti-FMD virus antibodies in the colostrum. This maternally-derived antibody (MDA) provides immediate protection against infection with FMD virus, but also interferes with the development of active immunity following vaccination. However, susceptibility to infection precedes the ability to respond to vaccination in the presence of MDA. Currently available vaccines cannot overcome this inhibitory effect of MDA, and protection of young stock can only be provided by their- isolation from FMD virus.


id: cord-327287-e5k2gcse
title: The challenges of diagnosing heparin‐induced thrombocytopenia in patients with COVID‐19
author: May, Jori E.
date: 2020-08-02
txt: ./txt/cord-327287-e5k2gcse.txt
cache: ./cache/cord-327287-e5k2gcse.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/32838112/
doi: 10.1002/rth2.12416
abstract: nan
summary:
  key: cord-327287-e5k2gcse authors: May, Jori E.; Siniard, Rance C.; Marques, Marisa title: The challenges of diagnosing heparin‐induced thrombocytopenia in patients with COVID‐19 cord_uid: e5k2gcse To the Editor, Riker EIAs are sensitive, but not specific, for HIT diagnosis because they detect all anti-platelet factor 4 (PF4)/heparin antibodies, including those that are nonpathogenic. 3 In contrast, functional assays (including SRA) identify only antibodies with the pathogenic ability to activate platelets and therefore have increased specificity. 3 Given that severe COVID-19 is a hyperinflammatory state, it is plausible that the increased immunoreactivity also increases production of anti-PF4/heparin antibodies; however, they may not result in clinical HIT but may instead increase potential for false-positive EIAs. Herein, we report our experience with hospitalized patients with The authors have no conflicts of interest to disclose. Heparin-induced thrombocytopenia with thrombosis in COVID-19 adult respiratory distress syndrome COVID-19 and its implications for thrombosis and anticoagulation Testing for heparin-induced thrombocytopenia antibodies


id: cord-327629-ep28ay11
author: Herron, J.B.T.
date: 2020-06-20
txt: ./txt/cord-327629-ep28ay11.txt
cache: ./cache/cord-327629-ep28ay11.txt
extension: .txt
mime: text/plain
url: https://www.sciencedirect.com/science/article/pii/S0266435620302801?v=s5
doi: 10.1016/j.bjoms.2020.06.021
summary:
  authors: Herron, J.B.T.; Dennis, J.; Brennan, P.A. title: Coronavirus antibody positive tests and continued use of personal protective equipment throughout the pandemic Antibody testing has rapidly been deployed but it is creating challenges for staff and patients. Mask use has come to the forefront and human factor (HF) strategies must be examined to reduce risk associated with lack of engagement from both healthcare staff and patients. Suggested plans have included developing a cohort of immune staff to care for COVID-19 patients allowing for a relaxation of overstretched personal protection equipment (PPE) resources. Masks reduce nosocomial spread and are important, particularly for healthcare staff (19) . For the antibody test, even after the exact nature of protection is determined, basic public health measures are not forgotten and that staff feel able to challenge those in more authoritative positions regarding PPE. Personal protective equipment and Covid 19-a risk to healthcare staff?

title:
  Coronavirus antibody positive tests and continued use of personal protective equipment throughout the pandemic

abstract:
  The COVID-19 pandemic has thrust not only a novel virus onto the world, but new challenges resulting in novel approaches. Governments have reduced regulation in order to facilitate timely advances to combat the disease. Antibody testing has rapidly been deployed but it is creating challenges for staff and patients. Mask use has come to the forefront and human factor (HF) strategies must be examined to reduce risk associated with lack of engagement from both healthcare staff and patients. In this we explore these issues and suggest some solutions.


id: cord-327883-s9nbr5y8
title: Section Virology
author: nan
date: 1990-03-31
txt: ./txt/cord-327883-s9nbr5y8.txt
cache: ./cache/cord-327883-s9nbr5y8.txt
extension: .txt
mime: text/plain
url: https://www.sciencedirect.com/science/article/pii/S0934884011800393
doi: 10.1016/s0934-8840(11)80039-3
abstract: nan
summary:
  By improving the enzyme-linked immunosorbent assay (ELISA) for HSV-2-antibodies and additional testing of sera by Western blot, we were able to specifically identify HSV-l-and HSV-2-antibodies in serum samples. To get some insight into the molecular basis of processes controlling the viral expression we studied the sequence-specific DNA-protein interactions within the genomic regulatory regions. for Med. Microbiology, Univ., D-5300 Bonn Semiquantitative detection of Hepatitis B Virus (HBV) DNA in sera of infected individuals has become an important means of modern serological hepatitis diagnostics. THOMSSEN 1 In the course of acute Epstein-Barr virus (EBV) infection IgM antibodies always occur against two cellular antigens that were characterized as proteins with a molecular weight of 26 kD (p26) and 29 kD (p29), respectively. The frequency and specificity of antibodies to P-gene encoded proteins of human hepatitis B virus was tested in sera of acute and chronically infected patients with and without hepatocellular carcinoma (HCC).


id: cord-328753-qwdxgk4z
title: Use of camel single-domain antibodies for the diagnosis and treatment of zoonotic diseases
author: Lafaye, Pierre
date: 2018-09-25
txt: ./txt/cord-328753-qwdxgk4z.txt
cache: ./cache/cord-328753-qwdxgk4z.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1016/j.cimid.2018.09.009
doi: 10.1016/j.cimid.2018.09.009
summary:
  The antigen-binding region of such homodimeric heavy-chain only antibodies consists of one single domain, called VHH. VHHs provide many advantages over conventional full-sized antibodies and currently used antibody-based fragments (Fab, scFv), including high specificity, stability and solubility, and small size, allowing them to recognize unusual antigenic sites and deeply penetrate tissues. The active antigen-binding fragment of heavy chain antibodies can be cloned and expressed in the form of VHH, which consists of only one domain (Fig. 1) . Gene therapy with an adenoviral vector expressing a bispecific VHH, consisting of two linked VHHs targeting different PA-neutralizing epitopes, was tested in mice, and found to protect them from anthrax toxin challenge and anthrax spore infection [55] . [92] have been found in the sera of infected camels, whereas antibodies against rabies virus, vesicular stomatitis virus, and FMD virus have been detected in llamas [93] and could lead to the possible isolation of specific broadly neutralizing VHHs. Many neutralizing VHHs that bind to different sites on the same target, including hidden antigenic sites, can be isolated from immunized or infected camelids.

abstract:
  Camelids produce both conventional heterotetrameric antibodies and homodimeric heavy-chain only antibodies. The antigen-binding region of such homodimeric heavy-chain only antibodies consists of one single domain, called VHH. VHHs provide many advantages over conventional full-sized antibodies and currently used antibody-based fragments (Fab, scFv), including high specificity, stability and solubility, and small size, allowing them to recognize unusual antigenic sites and deeply penetrate tissues. Since their discovery, VHHs have been used extensively in diagnostics and therapy. In recent decades, the number of outbreaks of diseases transmissible from animals to humans has been on the rise. In this review, we evaluate the status of VHHs as diagnostic and therapeutic biomolecular agents for the detection and treatment of zoonotic diseases, such as bacterial, parasitic, and viral zoonosis. VHHs show great adaptability to inhibit or neutralize pathogenic agents for the creation of multifunctional VHH-based diagnostic and therapeutic molecules against zoonotic diseases.


id: cord-328935-mn8r972x
title: Mucosal Veterinary Vaccines: Comparative Vaccinology
author: Hodgins, Douglas C.
date: 2015-03-13
txt: ./txt/cord-328935-mn8r972x.txt
cache: ./cache/cord-328935-mn8r972x.txt
extension: .txt
mime: text/plain
url: https://api.elsevier.com/content/article/pii/B9780124158474000689
doi: 10.1016/b978-0-12-415847-4.00068-9
summary:
  Studies of the potential of novel adjuvants to improve vaccine efficacy against genetically unstable, immune-subverting RNA viruses, such as porcine reproductive and respiratory syndrome virus in pigs, should assist in the control of pathogens with similar characteristics in other species. However, a recent study showed that an inactivated reassortant RV strain (CDC-9 strain) formulated with aluminum phosphate and administered systemically in gnotobiotic pigs resulted in induction of serum IgG antibody titers, coinciding with partial protection against shedding and diarrhea, suggesting that adjuvant may have stimulated local specific (gut IgA antibodies) or nonspecific immune responses, which were not assessed in this study (Wang et al., 2010) . Intranasal delivery of whole cell lysate of Mycobacterium tuberculosis induces protective immune responses to a modified live porcine reproductive and respiratory syndrome virus vaccine in pigs

abstract:
  Infections of mucosal surfaces are major causes of morbidity, mortality, and economic loss in species of veterinary interest, and a concern for animal welfare. Vaccines are used extensively in veterinary medicine, and innovative vaccine technologies such as recombinant DNA-vectored and distinguishing infected from vaccinated animals (DIVA) vaccines and automated in ovo vaccination (of embryonated chicken eggs) have been rapidly adopted commercially. Immunological research using outbred, nonrodent animal models has contributed to a broader understanding of mucosal defenses, and has provided the initial impetus for investigation of the common mucosal immune system. Studies of the potential of novel adjuvants to improve vaccine efficacy against genetically unstable, immune-subverting RNA viruses, such as porcine reproductive and respiratory syndrome virus in pigs, should assist in the control of pathogens with similar characteristics in other species. Successful development of vaccines to prevent and treat ascending infections of the reproductive tract of cattle set a precedent for applications in other species including humans. Studies of mucosal adjuvants and delivery systems continue at the interface between passive and active immunity, with the goal of inducing the earliest possible protection against enteric and respiratory pathogens of neonates.


id: cord-329857-pcsuu597
author: Chan, Kuan Rong
date: 2015-11-02
txt: ./txt/cord-329857-pcsuu597.txt
cache: ./cache/cord-329857-pcsuu597.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/26466016/
doi: 10.1586/14787210.2015.1079127
summary:
  The binding affinity of antibodies to viruses can directly impact the efficacy of mAbs [4] , suggesting that target-specific mechanisms likely account for much of the efficacy of therapeutic mAbs. However, many studies have also highlighted the contribution of Fc-mediated immune effector functions in modulating the efficacy of these mAbs [5] . FcgRs have been shown to be important in modulating the efficacy of therapeutic mAbs [5] due to their involvement in FcgRmediated phagocytosis, cytokine production, ADCC and complement-dependent cytotoxicity (CDC) that aids in virus neutralization (FIGURE 1). Given the importance of FcgRs in mediating virus neutralization and Fc effector functions, a better understanding of how therapeutic antibodies neutralize virus infections in FcgRbearing cells will impact implementation of dosing regiments and allow development of improved therapeutic antibodies against infectious diseases. Given the importance of Fc-FcgR interaction in antibodymediated effector functions, Fc modification could lead to the development of therapeutic antibodies with improved interaction to activating FcgRs. This could enhance FcgR-mediated uptake, cytokine production, antigen presentation, ADCC and CDC.

title:
  Fc receptors and their influence on efficacy of therapeutic antibodies for treatment of viral diseases

abstract:
  The lack of vaccines against several important viral diseases necessitates the development of therapeutics to save lives and control epidemics. In recent years, therapeutic antibodies have received considerable attention due to their good safety profiles and clinical success when used against viruses such as respiratory syncytial virus, Ebola virus and Hendra virus. The binding affinity of these antibodies can directly impact their therapeutic efficacy. However, we and others have also demonstrated that the subtype of Fc-gamma receptors (FcγRs) engaged influences the stoichiometric requirement for virus neutralization. Hence, the development of therapeutic antibodies against infectious diseases should consider the FcγRs engaged and Fc-effector functions involved. This review highlights the current state of knowledge about FcγRs and FcγR effector functions involved in virus neutralization, with emphasis on factors that can affect FcγR engagement. A better understanding of Fc-FcγR interactions during virus neutralization will allow development of therapeutic antibodies that are efficacious and can be administered with minimal side effects.


id: cord-330218-l5q3n3ri
title: TRIM21: a cytosolic Fc receptor with broad antibody isotype specificity
author: Foss, Stian
date: 2015-10-26
txt: ./txt/cord-330218-l5q3n3ri.txt
cache: ./cache/cord-330218-l5q3n3ri.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/26497531/
doi: 10.1111/imr.12363
summary:
  Neutralization of viruses by antibodies is predicted to depend on high-affinity binding to specific epitopes of surface-exposed viral proteins that are required for binding to target cell receptors (4) . These effector functions are induced upon binding of antibody-virus immune complexes to classical Fc c receptors (FccRs) expressed on the surface of hematopoietic cells such as natural killer (NK) cells, macrophages, and dendritic cells, which results in clearance and induction of T-cell responses (8) . Low antibody-virus stoichiometry may also result in inefficient FccR-mediated effector functions by immune cells as efficient phagocytosis requires the formation of immune complexes and cross-binding to cell-surface FccRs. In addition, as TRIM21 also engages IgM and IgA, it is likely to contribute to early protection, and at the gate of entry of most viral pathogens, the mucosal barrier.

abstract:
  Antibodies are key molecules in the fight against infections. Although previously thought to mediate protection solely in the extracellular environment, recent research has revealed that antibody-mediated protection extends to the cytosolic compartment of cells. This postentry viral defense mechanism requires binding of the antibody to a cytosolic Fc receptor named tripartite motif containing 21 (TRIM21). In contrast to other Fc receptors, TRIM21 shows remarkably broad isotype specificity as it does not only bind IgG but also IgM and IgA. When viral pathogens coated with these antibody isotypes enter the cytosol, TRIM21 is rapidly recruited and efficient neutralization occurs before the virus has had the time to replicate. In addition, inflammatory signaling is induced. As such, TRIM21 acts as a cytosolic sensor that engages antibodies that have failed to protect against infection in the extracellular environment. Here, we summarize our current understanding of how TRIM21 orchestrates humoral immunity in the cytosolic environment.


id: cord-330324-4hqhty5o
author: Yu, Meng
date: 2008-02-29
txt: ./txt/cord-330324-4hqhty5o.txt
cache: ./cache/cord-330324-4hqhty5o.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1016/j.jim.2007.11.009
doi: 10.1016/j.jim.2007.11.009
summary:
  title: Determination and application of immunodominant regions of SARS coronavirus spike and nucleocapsid proteins recognized by sera from different animal species In this study, we aim to search for and compare immunodominant regions of the spike (S) and nucleocapsid (N) proteins which are recognized by sera from different animal species, including mouse, rat, rabbit, civet, pig and horse. In this study we identified and characterized the major immunodominant domains of the SARS-CoV N and S proteins recognized by different animal species, and then developed competition ELISAs based on these findings. The specificity of the antibody was further confirmed using Western blot against viral antigen (data not shown) and IFAT using SARS-CoV infected Vero cells. One of the main aims of this study was to assess the feasibility of developing a competition ELISA for detection of SARS-CoV antibodies from different animal species. Inhibition of binding of mono-specific chicken antibodies to SARS-CoV by sera from different species.

title:
  Determination and application of immunodominant regions of SARS coronavirus spike and nucleocapsid proteins recognized by sera from different animal species

abstract:
  Abstract Knowledge of immunodominant regions in major viral antigens is important for rational design of effective vaccines and diagnostic tests. Although there have been many reports of such work done for SARS–CoV, these were mainly focused on the immune responses of humans and mice. In this study, we aim to search for and compare immunodominant regions of the spike (S) and nucleocapsid (N) proteins which are recognized by sera from different animal species, including mouse, rat, rabbit, civet, pig and horse. Twelve overlapping recombinant protein fragments were produced in Escherichia coli, six each for the S and N proteins, which covered the entire coding region of the two proteins. Using a membrane-strip based Western blot approach, the reactivity of each antigen fragment against a panel of animal sera was determined. Immunodominant regions containing linear epitopes, which reacted with sera from all the species tested, were identified for both proteins. The S3 fragment (aa 402–622) and the N4 fragment (aa 220–336) were the most immunodominant among the six S and N fragments, respectively. Antibodies raised against the S3 fragment were able to block the binding of a panel of S-specific monoclonal antibodies (mAb) to SARS–CoV in ELISA, further demonstrating the immunodominance of this region. Based on these findings, one-step competition ELISAs were established which were able to detect SARS–CoV antibodies from human and at least seven different animal species. Considering that a large number of animal species are known to be susceptible to SARS–CoV, these assays will be a useful tool to trace the origin and transmission of SARS–CoV and to minimise the risk of animal-to-human transmission.


id: cord-331786-wgt7kg6f
author: Diego-Martin, Borja
date: 2020-10-13
txt: ./txt/cord-331786-wgt7kg6f.txt
cache: ./cache/cord-331786-wgt7kg6f.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1101/2020.10.13.331306
doi: 10.1101/2020.10.13.331306
summary:
  For this purpose, we tested our ability to produce, in the framework of an academic lab and in a matter of weeks, milligram amounts of six different recombinant monoclonal antibodies against SARS-CoV-2 in Nicotiana benthamiana. In parallel, we also produced the recombinant SARS-CoV-2 N protein and its Receptor Binding Domain (RBD) in planta and used them to test the binding specificity of the recombinant mAbs. Finally, for two of the antibodies we assayed a simple scale-up production protocol based on the extraction of apoplastic fluid. Finally, we performed sandwich ELISA tests of sybody17 and nanobody72 ( Fig 5E and Fig 5F, respectively) using the total and concentrated apoplastic fluid as detection reagent against serial dilutions of crude plant extracts from RBD-producing plants, showing that this simple antibody preparation can be directly employed in detection procedures without the need of additional purification steps.

title:
  Pilot production of SARS-CoV-2 related proteins in plants: a proof of concept for rapid repurposing of indoors farms into biomanufacturing facilities

abstract:
  The current CoVid-19 crisis is revealing the strengths and the weaknesses of the world’s capacity to respond to a global health crisis. A critical weakness has resulted from the excessive centralization of the current biomanufacturing capacities, a matter of great concern, if not a source of nationalistic tensions. On the positive side, scientific data and information have been shared at an unprecedented speed fuelled by the preprint phenomena, and this has considerably strengthened our ability to develop new technology-based solutions. In this work we explore how, in a context of rapid exchange of scientific information, plant biofactories can serve as a rapid and easily adaptable solution for local manufacturing of bioreagents, more specifically recombinant antibodies. For this purpose, we tested our ability to produce, in the framework of an academic lab and in a matter of weeks, milligram amounts of six different recombinant monoclonal antibodies against SARS-CoV-2 in Nicotiana benthamiana. For the design of the antibodies we took advantage, among other data sources, of the DNA sequence information made rapidly available by other groups in preprint publications. mAbs were all engineered as single-chain fragments fused to a human gamma Fc and transiently expressed using a viral vector. In parallel, we also produced the recombinant SARS-CoV-2 N protein and its Receptor Binding Domain (RBD) in planta and used them to test the binding specificity of the recombinant mAbs. Finally, for two of the antibodies we assayed a simple scale-up production protocol based on the extraction of apoplastic fluid. Our results indicate that gram amounts of anti-SARS-CoV-2 antibodies could be easily produced in little more than 6 weeks in repurposed greenhouses with little infrastructure requirements using N. benthamiana as production platform. Similar procedures could be easily deployed to produce diagnostic reagents and, eventually, could be adapted for rapid therapeutic responses.


id: cord-335121-ro3x3qa3
author: Ingram, George A.
date: 1988-04-30
txt: ./txt/cord-335121-ro3x3qa3.txt
cache: ./cache/cord-335121-ro3x3qa3.txt
extension: .txt
mime: text/plain
url: https://api.elsevier.com/content/article/pii/0020751988901476
doi: 10.1016/0020-7519(88)90147-6
summary:
  Abstract Antibodies against Crithidia fasciculata choanomastigotes were detected in green toad (Bufo viridis) sera by direct agglutination, indirect haemagglutination (IHA), complement-fixation test (CFT) and enzyme-linked immunosorbent assay (ELISA), Correlation coefficients (r) were calculated for comparisons between each of the techniques and regression formulae derived in order to convert antibody levels as determined by one immunological method to that of another. In this paper we present the results of acomparative assessment of four serological tests (direct agglutination, indirect haemagglutination, complement-fixation test and ELISA) used to detect and to determine the levels of antibodies in the sera of green toads (B. fasciculata and the number of control and immune sera containing detectable antibodies were the lowest for DA and CFT, intermediate for IHA and highest for the ELISA method (Table 1) . Nevertheless the method of antigen preparation ma> not be a salient criterion for antibody estimation in immune sera because correlation values of over 89% (f''< 0.001) were found when IHA titres were compared to those of ELISA.

title:
  A comparative assessment of four serological methods used in the detection and measurement of anti-parasite antibodies in the serum of the amphibian, bufo viridis

abstract:
  Abstract Antibodies against Crithidia fasciculata choanomastigotes were detected in green toad (Bufo viridis) sera by direct agglutination, indirect haemagglutination (IHA), complement-fixation test (CFT) and enzyme-linked immunosorbent assay (ELISA), Correlation coefficients (r) were calculated for comparisons between each of the techniques and regression formulae derived in order to convert antibody levels as determined by one immunological method to that of another. The highest mean titre obtained by ELISA was approximately 1.5–3.5 times greater than those obtained by the other techniques whilst CFT gave the lowest values. IHA and ELISA titres were affected by different preparations of the crithidial antigen extracts. Highly significant r values were determined for control sera when IHA was compared to ELISA (r > 0.79), and to both CFT and ELISA with immune animals (r > 0.96). ELISA would seem most applicable for screening other lower vertebrates for anti-parasite antibodies especially in areas of human disease prevalence.


id: cord-335311-l73hsik0
title: The role of phage display in therapeutic antibody discovery
author: Chan, Conrad E. Z.
date: 2014-08-18
txt: ./txt/cord-335311-l73hsik0.txt
cache: ./cache/cord-335311-l73hsik0.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/25135889/
doi: 10.1093/intimm/dxu082
summary:
  The defining attribute of all phage display libraries is the physical linking of antibody phenotype (specificity and affinity) with genotype (sequence) via the phage particle-this allows for in vitro selection on immobilized antigen or whole cells (Fig. 2) . In particular, a phage library constructed with the heavy chain CDR3 enriched for basic residues to improve binding to negatively charged carbohydrates produced anti-carbohydrate antibodies that had relatively high affinity (K D ≈ 50 nM) and excellent specificity (40) . Phage display is also likely to remain useful for discovery of antibodies against non-protein targets, evolution of dual-binding antibodies and for affinity maturation, due to the limitations of the natural immune system. Comparison of the efficiency of antibody selection from semi-synthetic scFv and non-immune Fab phage display libraries against protein targets for rapid development of diagnostic immunoassays The human combinatorial antibody library HuCAL GOLD combines diversification of all six CDRs according to the natural immune system with a novel display method for efficient selection of high-affinity antibodies

abstract:
  Phage display involves the expression of selected proteins on the surface of filamentous phage through fusion with phage coat protein, with the genetic sequence packaged within, linking phenotype to genotype selection. When combined with antibody libraries, phage display allows for rapid in vitro selection of antigen-specific antibodies and recovery of their corresponding coding sequence. Large non-immune and synthetic human libraries have been constructed as well as smaller immune libraries based on capturing a single individual’s immune repertoire. This completely in vitro process allows for isolation of antibodies against poorly immunogenic targets as well as those that cannot be obtained by animal immunization, thus further expanding the utility of the approach. Phage antibody display represents the first developed methodology for high throughput screening for human therapeutic antibody candidates. Recently, other methods have been developed for generation of fully human therapeutic antibodies, such as single B-cell screening, next-generation genome sequencing and transgenic mice with human germline B-cell genes. While each of these have their particular advantages, phage display has remained a key methodology for human antibody discovery due its in vitro process. Here, we review the continuing role of this technique alongside other developing technologies for therapeutic antibody discovery.


id: cord-335316-x2t5h5gu
author: Madariaga, M. L. L.
date: 2020-06-23
txt: ./txt/cord-335316-x2t5h5gu.txt
cache: ./cache/cord-335316-x2t5h5gu.txt
extension: .txt
mime: text/plain
url: http://medrxiv.org/cgi/content/short/2020.06.21.20132944v1?rss=1
doi: 10.1101/2020.06.21.20132944
summary:
  This was a prospective open label clinical study to assess the feasibility, safety and immunological impact of delivering anti-SARS-CoV-2 convalescent plasma to hospitalized patients aged 18 years or older with severe or life-threatening COVID-19 disease within 21 days from the onset of their illness. Univariate regression analysis for antibody titer (anti-RBD and anti-spike) was conducted against age, sex, body mass index (BMI), previous pregnancy, previous blood donation, blood type, symptoms (fever, cough, sore throat, dyspnea, abdominal pain, aguesia, anosmia, fatigue, myalgia, headache), co-morbidities (respiratory, cardiovascular, renal, diabetes, autoimmune disease, cancer, liver disease), smoking history, travel in the past 3 months to the United States, Asia or Europe, symptom duration, interval from symptoms resolution to plasma donation, and hospitalization. To determine predictors of anti-RBD and anti-spike antibody titer, we performed best subset multivariable analysis including age, sex, blood type, history of previous blood donation, fever, cough, fatigue, myalgia, symptom duration, hospitalization and travel in the United States within the past 3 months.

title:
  Clinical predictors of donor antibody titer and correlation with recipient antibody response in a COVID-19 convalescent plasma clinical trial

abstract:
  Background: Convalescent plasma therapy for COVID-19 relies on the transfer of anti-viral antibody from donors to recipients via plasma transfusion. The relationship between clinical characteristics and antibody response to COVID-19 is not well defined. We investigated predictors of convalescent antibody production and quantified recipient antibody response in a convalescent plasma therapy clinical trial. Methods: Multivariable analysis of clinical and serological parameters in 103 confirmed COVID-19 convalescent plasma donors 28 days or more following symptom resolution was performed. Mixed effects regression models with piecewise linear trends were used to characterize serial antibody responses in 10 convalescent plasma recipients with severe COVID-19. Results: Mean symptom duration of plasma donors was 11.9 and 7.8% (8/103) had been hospitalized. Antibody titers ranged from 0 to 1:3,892 (anti-receptor binding domain (RBD)) and 0 to 1:3,289 (anti-spike). Multivariable analysis demonstrated that higher anti-RBD and anti-spike titer were associated with increased age, hospitalization for COVID-19, fever, and absence of myalgia (all p<0.05). Fatigue was significantly associated with anti-RBD (p=0.03) but not anti-spike antibody titer (p=0.11). In pairwise comparison among ABO blood types, AB donors had higher anti-RBD titer than O negative donors (p=0.048) and higher anti-spike titer than O negative (p=0.015) or O positive (p=0.037) donors. Eight of the ten recipients were discharged, one remains on ECMO and one died on ECMO. No toxicity was associated with plasma transfusion. After excluding two ECMO patients and adjusting for donor antibody titer, recipient anti-RBD antibody titer increased on average 31% per day during the first three days post-transfusion (p=0.01) and anti-spike antibody titer by 40.3% (p=0.02). Conclusion: Advanced age, fever, absence of myalgia, fatigue, blood type and hospitalization were associated with higher convalescent antibody titer to COVID-19. Despite variability in donor titer, 80% of convalescent plasma recipients showed significant increase in antibody levels post-transfusion. A more complete understanding of the dose-response effect of plasma transfusion among COVID-19 patients is needed to determine the clinical efficacy of this therapy.


id: cord-336280-tsx409e3
author: Byrne, Barry
date: 2009-06-05
txt: ./txt/cord-336280-tsx409e3.txt
cache: ./cache/cord-336280-tsx409e3.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/22408533/
doi: 10.3390/s90604407
summary:
  Particular emphasis is placed on the detection of foodborne bacterial pathogens, such as Escherichia coli and Listeria monocytogenes, and additional examples relating to the monitoring of fungal pathogens, viruses, mycotoxins, marine toxins and parasites are also provided. It describes the development of electrochemical, potentiometric, piezoelectric and optical platforms for the monitoring of foodborne bacterial pathogens by incorporating monoclonal, polyclonal or recombinant antibodies in a variety of different assay formats. Polyclonal antibodies (pAb) are typically raised in rabbits, goats or sheep [29] , and their popularity is illustrated by the fact that they are frequently selected in immunosensor-based assays for pathogen detection. Hence, the selection of a highly-specific epitope on the pathogen is a key consideration, since many bacterial strains share homologues of surface-presented proteins which can lead to the detection of multiple cell-types by a single antibody. Muhammad-Tahir and Alocilja [74] developed a conductimetric biosensor incorporating a polyclonal antibody-based sandwich assay format in which the detection antibody was labelled with polyaniline.

title:
  Antibody-Based Sensors: Principles, Problems and Potential for Detection of Pathogens and Associated Toxins

abstract:
  Antibody-based sensors permit the rapid and sensitive analysis of a range of pathogens and associated toxins. A critical assessment of the implementation of such formats is provided, with reference to their principles, problems and potential for ‘on-site’ analysis. Particular emphasis is placed on the detection of foodborne bacterial pathogens, such as Escherichia coli and Listeria monocytogenes, and additional examples relating to the monitoring of fungal pathogens, viruses, mycotoxins, marine toxins and parasites are also provided.


id: cord-337464-otwps68u
author: Parray, Hilal Ahmed
date: 2020-05-27
txt: ./txt/cord-337464-otwps68u.txt
cache: ./cache/cord-337464-otwps68u.txt
extension: .txt
mime: text/plain
url: https://api.elsevier.com/content/article/pii/S156757692031105X
doi: 10.1016/j.intimp.2020.106639
summary:
  Even with the recent development of high throughput mAb generation technologies, hybridoma is the most favoured method due to its indigenous nature to preserve natural cognate antibody pairing information and preserves innate functions of immune cells. This review also summarizes the challenges and recent progress associated with hybridoma development, and how it has been overcome in these years to provide new insights for the isolation of mAbs. Antibodies are the glycoproteins produced by the B-cells also known as immunoglobulins, which are present in higher eukaryotes. The mice hybridoma technology is a multi-step process that takes advantage of a host animal''s natural ability to produce highly specific, high-affinity and fully functional mAbs. It involves the development and optimization of specific immunogenic antigen (Ag).

title:
  Hybridoma technology a versatile method for isolation of monoclonal antibodies, its applicability across species, limitations, advancement and future perspectives

abstract:
  The advancements in technology and manufacturing processes have allowed the development of new derivatives, biosimilar or advanced improved versions for approved antibodies each year for treatment regimen. There are more than 700 antibody-based molecules that are in different stages of phase I/II/ III clinical trials targeting new unique targets. To date, approximately more than 80 monoclonal antibodies (mAbs) have been approved. A total of 7 novel antibody therapeutics had been granted the first approval either in the United States or European Union in the year 2019, representing approximately 20% of the total number of approved drugs. Most of these licenced mAbs or their derivatives are either of hybridoma origin or their improvised engineered versions. Even with the recent development of high throughput mAb generation technologies, hybridoma is the most favoured method due to its indigenous nature to preserve natural cognate antibody pairing information and preserves innate functions of immune cells. The recent advent of antibody engineering technology has superseded the species level barriers and has shown success in isolation of hybridoma across phylogenetically distinct species. This has led to the isolation of monoclonal antibodies against human targets that are conserved and non-immunogenic in the rodent. In this review, we have discussed in detail about hybridoma technology, its expansion towards different animal species, the importance of antibodies isolated from different animal sources that are useful in biological applications, advantages, and limitations. This review also summarizes the challenges and recent progress associated with hybridoma development, and how it has been overcome in these years to provide new insights for the isolation of mAbs.


id: cord-338517-1mxcssjj
title: Antibody response to SARS‐Co‐V‐2, diagnostic and therapeutic implications
author: Ishay, Yuval
date: 2020-08-26
txt: ./txt/cord-338517-1mxcssjj.txt
cache: ./cache/cord-338517-1mxcssjj.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1002/hep4.1600
doi: 10.1002/hep4.1600
summary:
  The phage display method, allowing rapid and wide display of proteins directly correlated to their associated genes, can detect NAbs against SARS-CoV from both naïve and immune antibody libraries, capable of blocking the binding of S1 domain, thereby showing virus neutralization and prophylaxis capability either in vitro or in the animal models (31, 33, 36) . Another method, possibly allowing the production and utilization of existing NAbs, may include the use of Epstein-Barr virus (EBV) transformation of human B cells to improve the isolation of NAbs from the memory B cells harvested from the SARS-CoV infected patients (11) . Experimental and clinical data on the use of convalescent plasma products and humanized monoclonal antibodies for H5N1 influenza infection have also shown positive outcomes, and this treatment was proposed as a mean for overcoming anti-viral drug resistance (62, 79, 80) . In a study involving 20 patients with severe pandemic influenza A (H1N1) 2009 virus infection, administration of convalescent plasma reduced respiratory tract viral load, serum cytokine response, and mortality (81) .

abstract:
  The immune response against SARS‐CoV‐2 is comprised of both cellular and humoral arms. While current diagnostic methods are mainly based on PCR, they suffer from insensitivity. Therefore, antibody‐based serological tests are being developed to achieve higher sensitivity and specificity. Current efforts in treating SARS‐CoV‐2 infection include blocking of viral entry into the host cells, prohibiting viral replication and survival in the host cells, or reducing the exaggerated host immune response. Administration of convalescent plasma containing anti‐viral antibodies was proposed to improve the outcome in severe cases. In this paper, we review some of the aspects associated with the development of antibodies against SARS‐CoV‐2 and their potential use for improved diagnosis and therapy.


id: cord-339520-odly2fwg
author: Madic, J.
date: 1995-07-31
txt: ./txt/cord-339520-odly2fwg.txt
cache: ./cache/cord-339520-odly2fwg.txt
extension: .txt
mime: text/plain
url: https://api.elsevier.com/content/article/pii/0165242794053797
doi: 10.1016/0165-2427(94)05379-7
summary:
  Abstract Isotype-specific antibody responses to bovine herpesvirus 1 (BHV1) were measured in sera, nasal, ocular and genital secretions of calves that were reinfected with BHV1 and 6 weeks later treated with corticosteroids to reactivate putative latent virus. The control calves, which were infected for the first time, developed an IgM antibody response in serum, nasal and ocular secretions that was first detected on PRD 8 and lasted until PRD 27. Calves in which no virus excretion after reinfection and/or corticosteroid treatment was detected yet developed an antibody response against BHVl, mainly of the IgA isotype. However, it may be the serum IgA response seems to be a much more sensitive indicator for reinfection with or reactivation of BHVl than detection of nasal and ocular virus shedding. After corticosteroid treatment, virus-positive nasal secretions were detected in 20 of 26 reinfected calves, and a significant increase in serum IgGl and IgG2 antibody titre in 17 and 12 calves, respectively.

title:
  Isotype-specific antibody responses to bovine herpesvirus 1 in sera and mucosal secretions of calves after experimental reinfection and after reactivation

abstract:
  Abstract Isotype-specific antibody responses to bovine herpesvirus 1 (BHV1) were measured in sera, nasal, ocular and genital secretions of calves that were reinfected with BHV1 and 6 weeks later treated with corticosteroids to reactivate putative latent virus. After reinfection and after reactivation, no BHV1-specific IgM antibody response was detected. The serum IgA response was only transiently detectable after reinfection and again appeared rapidly after reactivation in most calves. Most calves showed an increase in nasal and ocular IgA titres after reinfection and reactivation; some calves also had IgA antibodies in genital secretions. A salient finding was that after reinfection and reactivation more calves showed a serum IgA response than virus shedding or an increase in serum IgG1 or IgG2 titres. This suggests that the serum IgA response would be the most sensitive indicator to detect BHV1 reinfection and reactivation. No correlation was found between nasal IgA titre at the time of reinfection or corticosteroid treatment and the period of virus shedding, suggesting that nasal IgA does not play a major role in protection against reinfection with BHV1.


id: cord-339879-92esdjy9
title: Phages and HIV-1: From Display to Interplay
author: Delhalle, Sylvie
date: 2012-04-13
txt: ./txt/cord-339879-92esdjy9.txt
cache: ./cache/cord-339879-92esdjy9.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/22606007/
doi: 10.3390/ijms13044727
summary:
  The BNtAb IgG1 b12 was the first neutralizing MAb selected from a phage-displayed Fab (antibody fragment composed of one constant and one variable domain of the heavy (CH1 and VH) and the light (CL and VL) chains linked together) library derived from an HIV-1-infected donor (See section 3.1.1.1.1.) [41] . At the end of the second round, selected phages displaying longer inserts of 40 to 50 AA corresponding to the N-and C-terminal regions of Gag were identified, revealing the presence of two distinct antigenic regions in Gag. This study demonstrated that gene-fragment phage display could be used to identify epitopes targeted by polyclonal Abs. Although they occur at a very low frequency in humans, antibodies targeting host proteins involved in HIV-1 infection have been reported in immunized animals. Anti-human immunodeficiency virus type 1 human monoclonal antibodies that bind discontinuous epitopes in the viral glycoproteins can identify mimotopes from recombinant phage peptide display libraries

abstract:
  The complex hide-and-seek game between HIV-1 and the host immune system has impaired the development of an efficient vaccine. In addition, the high variability of the virus impedes the long-term control of viral replication by small antiviral drugs. For more than 20 years, phage display technology has been intensively used in the field of HIV-1 to explore the epitope landscape recognized by monoclonal and polyclonal HIV-1-specific antibodies, thereby providing precious data about immunodominant and neutralizing epitopes. In parallel, biopanning experiments with various combinatorial or antibody fragment libraries were conducted on viral targets as well as host receptors to identify HIV-1 inhibitors. Besides these applications, phage display technology has been applied to characterize the enzymatic specificity of the HIV-1 protease. Phage particles also represent valuable alternative carriers displaying various HIV-1 antigens to the immune system and eliciting antiviral responses. This review presents and summarizes the different studies conducted with regard to the nature of phage libraries, target display mode and biopanning procedures.


id: cord-340305-jtvn9tlm
title: A Minimalist Strategy Towards Temporarily Defining Protection for COVID-19
author: Cimolai, Nevio
date: 2020-09-19
txt: ./txt/cord-340305-jtvn9tlm.txt
cache: ./cache/cord-340305-jtvn9tlm.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1007/s42399-020-00533-4
doi: 10.1007/s42399-020-00533-4
summary:
  At this time, the best correlates with protection from natural coronavirus infections are systemic neutralizing antibody and mucosal IgA. Others have found strong correlations between neutralizing antibodies and EIA-detected antibodies to various SARS-CoV-2 antigens [41, 42] .Some have found diversity in immune responses contingent on the nature of presenting disease [38, 43] . With the availability of viral antigen, most scientists in the know-how would be able to fashion a test for antibody determination in short order and most would likely choose an enzyme immunoassay (EIA) (or nearly equivalent non-enzymebased assay) for its potential of automation and widespread use. Sensitive and specific detection of low-level antibody responses in mild Middle East Respiratory Syndrome coronavirus infections A highly specific and sensitive serological assay detects SARS-CoV-2 antibody levels in COVID-19 patients that correlate with neutralization SARS-CoV-2 assays to detect functional antibody responses that block ACE2 recognition in vaccinated animals and infected patients

abstract:
  Until either efficacious therapy or vaccination for COVID-19 is achieved, there will be a need to regain world economic stability while yet controlling the pandemic with current approaches. For those infected thus far, there is a prevailing perspective that devising recognition for protective immunity will progressively allow segments of society to return to some functionality more than is existing. At this time, the best correlates with protection from natural coronavirus infections are systemic neutralizing antibody and mucosal IgA. Serum neutralizing antibody more easily fulfills the latter requisite, but current live virus methods for neutralization prevent large-scale application. It is conceivable that the exposure of previously infected individuals can allow for the definition of protective thresholds of neutralizing antibody. Thereafter, many other antibody assays will be able to screen for surrogate protection after correlations with protective neutralizing antibody are made. Specificity of common antibody tests would benefit from confirmatory blocking systems or confirmatory immunoblotting fingerprints with well-defined antigen(s). The opportunity for the scientific community to make these assessments is evident in the current context of the COVID-19 epidemic given the large numbers of infected individuals worldwide. Such information will also be vital to guide vaccine development and/or immunotherapy.


id: cord-341305-zf97tcwe
author: Ge, Shikun
date: 2020-09-03
txt: ./txt/cord-341305-zf97tcwe.txt
cache: ./cache/cord-341305-zf97tcwe.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1186/s13567-020-00832-7
doi: 10.1186/s13567-020-00832-7
summary:
  The CPV-VLP and CPV-VP2 protein showed similar reaction values to the purified scFv in the ELISA test, and the results of ELISA analysis using IgY-scFv toward CPV clinical samples were consistent with commercial immunochromatographic assay (ICA) and PCR detection, the scFv did not show cross reactivity with canine distemper virus (CDV) and canine coronavirus (CCV). This study revealed the feasibility of a novel functional antibody fragment development strategy by generating diversified avian IgY-scFv libraries towards the pathogenic target of interest for both detection and therapeutic purposes in veterinary medicine. Functional antibody fragments (i.e.: scFv, Fab) generated by phage-display technology have been not yet routinely evaluated and applied in the veterinary medicine despite it has been well confirmed that such engineered antibodies offer a series of advantages over polyclonal and full-length monoclonal antibodies.

title:
  Canine Parvovirus is diagnosed and neutralized by chicken IgY-scFv generated against the virus capsid protein

abstract:
  Canine parvovirus (CPV) can cause acute and highly contagious bloody enteritis in dog. To obtain antibodies against CPV, hens were immunized with virus-like particles (VLP) of CPV-VP2. The IgY single chain fragment variables (scFv) were generated by T7 phage display system and expressed in E. coli system. The titer of the primary scFv library reached to 1.5 × 10(6) pfu/mL, and 95% of the phages contained the target fragments. The CPV-VLP and CPV-VP2 protein showed similar reaction values to the purified scFv in the ELISA test, and the results of ELISA analysis using IgY-scFv toward CPV clinical samples were consistent with commercial immunochromatographic assay (ICA) and PCR detection, the scFv did not show cross reactivity with canine distemper virus (CDV) and canine coronavirus (CCV). IgY-scFv was successfully expressed in CRFK cells, and in the virus suppression assay, 55% of CPV infections were eliminated within 24 h. Docking results demonstrated that the number of amino acids of the binding sides between scFv and VP2 were AA37 and AA40, respectively. This study revealed the feasibility of a novel functional antibody fragment development strategy by generating diversified avian IgY-scFv libraries towards the pathogenic target of interest for both detection and therapeutic purposes in veterinary medicine.


id: cord-342242-cynpob7b
author: Godakova, Svetlana A.
date: 2019-08-07
txt: ./txt/cord-342242-cynpob7b.txt
cache: ./cache/cord-342242-cynpob7b.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.3390/toxins11080464
doi: 10.3390/toxins11080464
summary:
  Based on the analysis of B11-Fc and G3-Fc clones'' circulation time in the serum (presence of antibodies 14 days after injection), we decided to conduct an experiment on the survival of these mice, which previously received a single injection of the VHHs with the Fc fragment, with a repeated administration of only the lethal toxin dose 14 days after the original administration. Overall, we obtained numerous clones after two rounds of biopanning; we selected 15 clones for initial analysis based on their CDR3s, chose two clones (B11 and G3) with the best pre-mixed results in phage form in vivo, produced them in protein form, and modified their structure and characteristics by dimerization via a (Gly4Ser) 3 linker and fusion to a human IgG Fc fragment to enhance their protective activity.

title:
  Camelid VHHs Fused to Human Fc Fragments Provide Long Term Protection Against Botulinum Neurotoxin A in Mice

abstract:
  The bacterium Clostridium botulinum is the causative agent of botulism—a severe intoxication caused by botulinum neurotoxin (BoNT) and characterized by damage to the nervous system. In an effort to develop novel C. botulinum immunotherapeutics, camelid single-domain antibodies (sdAbs, VHHs, or nanobodies) could be used due to their unique structure and characteristics. In this study, VHHs were produced using phage display technology. A total of 15 different monoclonal VHHs were selected based on their comlementarity-determining region 3 (CDR3) sequences. Different toxin lethal dose (LD(50)) challenges with each selected phage clone were conducted in vivo to check their neutralizing potency. We demonstrated that modification of neutralizing VHHs with a human immunoglobulin G (IgG)1 Fc (fragment crystallizable) fragment (fusionbody, VHH-Fc) significantly increased the circulation time in the blood (up to 14 days). At the same time, VHH-Fc showed the protective activity 1000 times higher than monomeric form when challenged with 5 LD(50). Moreover, VHH-Fcs remained protective even 14 days after antibody administration. These results indicate that this VHH-Fc could be used as an effective long term antitoxin protection against botulinum type A.


id: cord-344445-slv7r9u7
author: Vakharia, Kunal
date: 2020-06-03
txt: ./txt/cord-344445-slv7r9u7.txt
cache: ./cache/cord-344445-slv7r9u7.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/32493712/
doi: 10.1136/medethics-2020-106467
summary:
  The discussion that has continued since the initial severe acute respiratory syndrome virus and avian influenza epidemics has focused on the potential for immunity among the general population and the moral obligation to treat that is often faced by healthcare professionals and institutions. With the growing literature and data suggesting the possibility of mutations, unequal impacts on different people and the potential repercussions of the spike protein for those with IgG immunity already, can society in good faith adopt a moral prerogative to put antibody-positive people in the front line? Healthcare workers form a group of individuals who recognise the potential of COVID-19, the impact it has had, and are still willing to go to work and continue to face the challenge. With limited knowledge about the significance of COVID-19 antibody testing at this time, it is hard to use this to stratify work in a healthcare setting or to use it for any purpose beyond epidemiological studies on the spread of the disease.

title:
  The right to know: ethical implications of antibody testing for healthcare workers and overlooked societal implications

abstract:
  After the initial surge in cases of coronavirus (COVID-19), the outbreak has been managed differently in different countries. In the USA, it has been managed in many different ways between states, cities and even counties. This disparity is slowly becoming more and more pronounced with the advent of antibody testing. Although many argue over the potential merits of antibody testing as an immunity passport to allow the economy to restart, there are other implications that stand at the heart of the bioethical debate that are often overlooked. Particularly with COVID-19, there are many uncertainties and the discourse alone of antibodies presumes misinformation that may outweigh the epidemiological benefits of antibody testing. Although this paper does not seek to eliminate antibody testing, it does highlight the need for appropriate counselling both on a personal level with each patient but on a more global level. This moral standard of appropriate education is key to allowing the continued autonomy needed during this pandemic.


id: cord-345296-4z7yfj5s
title: Neutralizing Antibody Response and SARS Severity
author: Ho, Mei-Shang
date: 2005-11-17
txt: ./txt/cord-345296-4z7yfj5s.txt
cache: ./cache/cord-345296-4z7yfj5s.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/16318725/
doi: 10.3201/eid1111.040659
summary:
  Using the Taiwan nationwide laboratory-confirmed severe acute respiratory syndrome (SARS) database, we analyzed neutralizing antibody in relation to clinical outcomes. Using the Taiwan nationwide laboratory-confirmed severe acute respiratory syndrome (SARS) database, we analyzed neutralizing antibody in relation to clinical outcomes. To adjust the time effects and other covariates of interest, the relationship between antibody titer, based on logarithmic transformation of base 2 (serum dilution) and other potential factors, i.e., age, sex, infection source, and duration of illness, was quantified by linear mixed models (18) , which took into account the correlation between repeated measurements of each study participants. In the model, patients with a more severe clinical course had earlier and higher antibody responses; we then examined the death rate of the early responders (Table 6 ). Organ distribution of severe acute respiratory syndrome (SARS) associated coronavirus (SARS-CoV) in SARS patients: implications for pathogenesis and virus transmission pathways

abstract:
  Using the Taiwan nationwide laboratory-confirmed severe acute respiratory syndrome (SARS) database, we analyzed neutralizing antibody in relation to clinical outcomes. With a linear mixed model, neutralizing antibody titer was shown to peak between week 5 and week 8 after onset and to decline thereafter, with a half-life of 6.4 weeks. Patients with a longer illness showed a lower neutralizing antibody response than patients with a shorter illness duration (p = 0.008). When early responders were compared with most patients, who seroconverted on and after week 3 of illness, the small proportion (17.4%) of early responders (antibody detectable within 2 weeks) had a higher death rate (29.6% vs. 7.8%) (Fisher exact test, p = 0.004), had a shorter survival time of <2 weeks (Fisher exact test, p = 0.013), and were more likely to be > 60 years of age (Fisher exact test, p = 0.01). Our findings have implications for understanding the pathogenesis of SARS and for SARS vaccine research and development.


id: cord-349669-o3eelqcw
author: Stadlbauer, Daniel
date: 2020-08-14
txt: ./txt/cord-349669-o3eelqcw.txt
cache: ./cache/cord-349669-o3eelqcw.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1111/trf.16047
doi: 10.1111/trf.16047
abstract: nan
summary:
  Convalescent plasma (CP) has presented another option, with its use and safety supported by numerous case series and retrospective studies [2] [3] [4] . Studies demonstrating antibody stability under refrigerated conditions have largely focused on peripheral blood samples stored for several days 7, 8 . Here, we demonstrate the long-term stability of anti-SARS-CoV-2 spike antibodies in donor CP samples collected at a local blood donor center for transfusion. After thawing of fifteen CP units, segments were sampled and anti-spike antibody titers were determined via enzyme-linked immunosorbent assays (ELISAs) 9 . While our study does not address the neutralization capacity of these antibodies, previous studies demonstrate significant correlation between spike antibody titers and neutralization capacity of plasma and serum samples 9 . Treatment of COVID-19 Patients with Convalescent Plasma Early safety indicators of COVID-19 convalescent plasma in 5,000 patients Convalescent plasma treatment of severe COVID-19: A matched control study Long-term stability of trastuzumab in plasma and whole blood samples stored under different conditions

title:
  Anti‐SARS‐CoV‐2 Spike Antibodies are Stable in Convalescent Plasma when Stored at 4° Celsius for at Least 6 Weeks


id: cord-350029-1y5ex4d5
title: Beyond serosurveys: Human biology and the measurement of SARS‐Cov‐2 antibodies
author: McDade, Thomas W.
date: 2020-08-09
txt: ./txt/cord-350029-1y5ex4d5.txt
cache: ./cache/cord-350029-1y5ex4d5.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1002/ajhb.23483
doi: 10.1002/ajhb.23483
abstract: nan
summary:
  Serological testing is a complementary approach that detects the presence of antibodies against SARS-CoV-2 in blood samples from exposed individuals (World Health Organization, 2020). If sufficient time has passed since the initial infection, the presence of IgM antibodies against SARS-CoV-2 antigens can be used to confirm a clinical case of COVID-19. In developing a low-cost ELISA for SARS-CoV-2 antibodies, our hope is that others can draw on the longstanding tradition of methodological innovation in human biology to promote community-based research on COVID-19. Human biologists are also well-positioned to consider a life course perspective on variation in outcomes in response to SARS-CoV-2 infection. Human biologists are uniquely positioned to make important contributions to our understanding of COVID-19, and methods that facilitate research in community-based settings globally will be central to that effort. Enzyme immunoassay for SARS-CoV-2 antibodies in dried blood spot samples: A minimally-invasive approach to facilitate community-and population-based screening


id: cord-352172-g0jiaenw
title: Protein microarrays: high-throughput tools for proteomics
author: Stoevesandt, Oda
date: 2014-01-09
txt: ./txt/cord-352172-g0jiaenw.txt
cache: ./cache/cord-352172-g0jiaenw.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/19385942/
doi: 10.1586/epr.09.2
summary:
  While conventionally made by the spotting of purified proteins, recent advances in technology have made it possible to produce protein microarrays through in situ cell-free synthesis directly from corresponding DNA arrays. Protein microarray technology has rapidly developed into one of the most active areas in biotechnology today, and is being increasingly applied for the high-throughput discovery of molecular interactions, profiling of protein expression and monitoring of protein modifications. While genome sequencing and annotations provide comprehensive information on protein-encoding genes, and DNA arrays analyze gene expression at the mRNA level, these technologies need to be complemented by functional proteomic studies in order to better understand protein activities, expression levels and interactions at the system level. A reverse-phase micro array approach has been successfully applied to discover distinct pathway-activation differences among breast cancer cell lines, demonstrating the use of array-based ana lysis for multiple pharmacodynamic biomarkers responding to targeted kinase inhibitors [108] .

abstract:
  Protein microarrays are versatile tools for parallel, miniaturized screening of binding events involving large numbers of immobilized proteins in a time- and cost-effective manner. They are increasingly applied for high-throughput protein analyses in many research areas, such as protein interactions, expression profiling and target discovery. While conventionally made by the spotting of purified proteins, recent advances in technology have made it possible to produce protein microarrays through in situ cell-free synthesis directly from corresponding DNA arrays. This article reviews recent developments in the generation of protein microarrays and their applications in proteomics and diagnostics.


id: cord-354137-6oe8nj1j
title: Aspects of recent development of immunosensors
author: Wang, Hua
date: 2008-05-20
txt: ./txt/cord-354137-6oe8nj1j.txt
cache: ./cache/cord-354137-6oe8nj1j.txt
extension: .txt
mime: text/plain
url: https://api.elsevier.com/content/article/pii/B9780123737380500118
doi: 10.1016/b978-012373738-0.50011-8
summary:
  Development of microfluidic immunosensor systems for proteomics and drug discovery have also been reported in recent years where the microfluidic system integrates multiple processes in a single device to improve analytical performance by reducing the reagent consumption and the analysis time, and increasing reliability and sensitivity through automation. A capacitive immunoassay based on antibody-embedded ultra-thin alumina sol-gel fi lms (∼20 to 40 nm) was reported and used for direct determination of antigens with a detection limit as low as ϳ1 ng mL Ϫ1 [92] . reported a successful integration of the lateral fl ow immunoassay format and impedance detection for prostate-specifi c antigen of tumor marker, where the electrochemical transducer was coated with a pH-sensitive polymer layer [93] . Based on the modifi cation of mixed SAMs on gold electrodes for covalently binding antigens, another piezoelectric immunosensor has been recently developed to detect antisperm antibody [153] .

abstract:
  This chapter focuses on the recent developments in the field of immunosensors. Immunosensors incorporate the specific immunochemical reaction with the modern transducers including electrochemical (potentiometric, conductometric, capacitative, impedance, amperometric), optical (fluorescence, luminescence, refractive index), and microgravimetric transducers. These immunosensor devices with dramatic improvements in the sensitivity and selectivity possess the abilities to investigate the reaction dynamics of antibody–antigen binding and the potential to revolutionize conventional immunoassay techniques. With the rapid development of immunological reagents and detection equipments, immunosensors have allowed an increasing range of analytes to be identified and quantified and in particular, simple-to-use, inexpensive, and reliable immunosensing systems have been developed for areas such as outpatient monitoring, large screening programs, and remote environmental surveillance. Immunosensors with lowered detection limits and increased sensitivities have been developed in various fields, particularly in clinical analysis. A noticeable development trend is also observed in the development of immunosensors combining with other techniques such as flow injection analysis (FIA) or capillary electrophoretic (CE) analysis, which complement and improve the present immunoassay methods. Belov et al. have proposed a novel immunophenotyping method for leukemias which uses a cluster of differentiation antibody microarray, and a microarray of enzyme-linked immunosorbent assay has been developed for autoimmune diagnosis of systematic rheumatic disease. Development of microfluidic immunosensor systems for proteomics and drug discovery have also been reported in recent years where the microfluidic system integrates multiple processes in a single device to improve analytical performance by reducing the reagent consumption and the analysis time, and increasing reliability and sensitivity through automation.


id: cord-354325-r73datur
title: Therapeutic Applications of Monoclonal Antibodies
author: Berger, Mitchell
date: 2002-07-31
txt: ./txt/cord-354325-r73datur.txt
cache: ./cache/cord-354325-r73datur.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/12120821/
doi: 10.1097/00000441-200207000-00004
summary:
  Attempts to use mouse myeloma cells to create hybrids and derive human MAbs led to the loss of human chromosomes and the inability to make human Igs. 13 Unfortunately, in vitro immunization is limited by its inability to produce a secondary response and by the absence of the affinity maturation process that occurs in vivo. In these transgenic mouse models, human antibodies with high affinity to an immunized antigen are naturally selected by the murine immune system via an affinity maturation process, and thereby show increased diversity of the MAbs. Transgenic mice may be a suitable alternative to chimeric or humanized antibody production or the use of phage display systems to create less immunogenic or novel antibodies. [43] [44] [45] Humanizing Monoclonal Antibodies Rodent MAbs with excellent affinities and specificities have been generated using conventional hybridoma technology, but their use in clinical medicine is limited due to the immune responses they elicit in humans.

abstract:
  ABSTRACT Researchers have sought therapeutic applications for monoclonal antibodies since their development in 1975. However, murine-derived monoclonal antibodies may cause an immunogenic response in human patients, reducing their therapeutic efficacy. Chimeric and humanized antibodies have been developed that are less likely to provoke an immune reaction in human patients than are murine-derived antibodies. Antibody fragments, bispecific antibodies, and antibodies produced through the use of phage display systems and genetically modified plants and animals may aid researchers in developing new uses for monoclonal antibodies in the treatment of disease. Monoclonal antibodies may have a number of promising potential therapeutic applications in the treatment of asthma, autoimmune diseases, cancer, poisoning, septicemia, substance abuse, viral infections, and other diseases.


id: cord-354700-bdpp3qmf
title: Dissecting human antibody responses: useful, basic and surprising findings
author: Lanzavecchia, Antonio
date: 2018-01-23
txt: ./txt/cord-354700-bdpp3qmf.txt
cache: ./cache/cord-354700-bdpp3qmf.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.15252/emmm.201808879
doi: 10.15252/emmm.201808879
summary:
  I will discuss how a target‐agnostic approach based on high‐throughput screening of antibodies produced by cultured B cells and plasma cells has not only provided potent and broadly neutralizing antibodies against a range of pathogens, but has also advanced our understanding of basic aspects of the immune response, from host–pathogen interaction to the role of somatic mutations in affinity maturation and in the diversification of the antibody response. I will discuss how a target-agnostic approach based on highthroughput screening of antibodies produced by cultured B cells and plasma cells has not only provided potent and broadly neutralizing antibodies against a range of pathogens, but has also advanced our understanding of basic aspects of the immune response, from host-pathogen interaction to the role of somatic mutations in affinity maturation and in the diversification of the antibody response.

abstract:
  Human memory B cells and plasma cells represent a rich source of antibodies that have been selected in response to human pathogens. In the last decade, different methods have been developed to interrogate the human memory repertoire and isolate monoclonal antibodies. I will discuss how a target‐agnostic approach based on high‐throughput screening of antibodies produced by cultured B cells and plasma cells has not only provided potent and broadly neutralizing antibodies against a range of pathogens, but has also advanced our understanding of basic aspects of the immune response, from host–pathogen interaction to the role of somatic mutations in affinity maturation and in the diversification of the antibody response. Most surprisingly, this approach has also revealed a new mechanism of diversification based on templated insertion of non‐Ig DNA into antibody genes that we discovered in the context of the immune response to malaria infection.


id: cord-354790-xx6imhzb
author: Lambour, Jennifer
date: 2016-08-17
txt: ./txt/cord-354790-xx6imhzb.txt
cache: ./cache/cord-354790-xx6imhzb.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1038/emi.2016.97
doi: 10.1038/emi.2016.97
summary:
  31 In addition to controlling the viral propagation by these mechanisms, the opsonization of viral particles and/or infected cells by therapeutic antiviral mAbs of the IgG type leads to the formation of immune complexes (ICs) recognizable by the FcγRs expressed on antigen-presenting cells (APCs) such as DCs. This can potentially affect the endogenous antiviral adaptive immune response of passive immunotherapy-treated individuals. Moreover, as the in vivo activity of anti-HIV-1 bNAbs, including viral load control, was recently shown to crucially depend on Fc effector functions, 53,54 an important issue is identifying that Fc-FcγRs interactions are involved in the induction of vaccinelike effects by antiviral mAbs. To understand the mechanisms underlying the enhancement of antiviral responses by ICs, several in vitro studies have addressed whether antibody-mediated viral uptake by DCs could lead to stronger activation of these cells and the development of stronger virus-specific CD4 + and CD8 + T-cell responses in an Fc-dependent manner.

title:
  Converting monoclonal antibody-based immunotherapies from passive to active: bringing immune complexes into play

abstract:
  Monoclonal antibodies (mAbs), which currently constitute the main class of biotherapeutics, are now recognized as major medical tools that are increasingly being considered to fight severe viral infections. Indeed, the number of antiviral mAbs developed in recent years has grown exponentially. Although their direct effects on viral blunting have been studied in detail, their potential immunomodulatory actions have been overlooked until recently. The ability of antiviral mAbs to modulate antiviral immune responses in infected organisms has recently been revealed. More specifically, upon recognition of their cognate antigens, mAbs form immune complexes (ICs) that can be recognized by the Fc receptors expressed on different immune cells of infected individuals. This binding may be followed by the modulation of the host immune responses. Harnessing this immunomodulatory property may facilitate improvements in the therapeutic potential of antiviral mAbs. This review focuses on the role of ICs formed with different viral determinants and mAbs in the induction of antiviral immune responses in the context of both passive immunotherapies and vaccination strategies. Potential deleterious effects of ICs on the host immune response are also discussed.


id: cord-355610-7xy4s483
author: Hu, Dan
date: 2019-06-26
txt: ./txt/cord-355610-7xy4s483.txt
cache: ./cache/cord-355610-7xy4s483.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/31242272/
doi: 10.1371/journal.ppat.1007836
summary:
  Here, by using sequential antigen panning of a yeast antibody library derived from healthy donors against the DENV envelop protein domain III (DIII) combined with depletion by an entry defective DIII mutant, we identified a cross-reactive human monoclonal antibody (mAb), m366.6, which bound with high affinity to DENV DIII from all four DENV serotypes. Furthermore, as the first germline-like mAb derived from a naïve antibody library that could neutralize all four DENV serotypes, the m366.6 can be a tool for exploring mechanisms of DENV infection, and is a promising therapeutic candidate. Its fully human origin, the germline-like nature, combined with high-affinity and broad neutralizing activity toward all DENV serotypes, suggest that m366.6 is a promising candidate antiviral agent and may also provide a unique template for designing effective dengue vaccine immunogens. Two antibodies, designated as m360 and m366, bound potently to DENV DIIIs. Their scFv gene were fused with human IgG1 Fc for protein expression, and surface plasmon resonance (SPR) experiments were used to evaluate the antigens binding.

title:
  A broadly neutralizing germline-like human monoclonal antibody against dengue virus envelope domain III

abstract:
  Dengue is the most widespread vector-borne viral disease caused by dengue virus (DENV) for which there are no safe, effective drugs approved for clinical use. Here, by using sequential antigen panning of a yeast antibody library derived from healthy donors against the DENV envelop protein domain III (DIII) combined with depletion by an entry defective DIII mutant, we identified a cross-reactive human monoclonal antibody (mAb), m366.6, which bound with high affinity to DENV DIII from all four DENV serotypes. Immunogenetic analysis indicated that m366.6 is a germline-like mAb with very few somatic mutations from the closest VH and Vλ germline genes. Importantly, we demonstrated that it potently neutralized DENV both in vitro and in the mouse models of DENV infection without detectable antibody-dependent enhancement (ADE) effect. The epitope of m366.6 was mapped to the highly conserved regions on DIII, which may guide the design of effective dengue vaccine immunogens. Furthermore, as the first germline-like mAb derived from a naïve antibody library that could neutralize all four DENV serotypes, the m366.6 can be a tool for exploring mechanisms of DENV infection, and is a promising therapeutic candidate.


