# pos

id: cord-324911-6s7ubbxl
pos: NNP
token:
  https://wellcome.ac.uk/press-release/unprecedented-international-consortiumassembled-accelerate-collaborative-multi-site

lemma:
  https://wellcome.ac.uk/press-release/unprecedented-international-consortiumassembled-accelerate-collaborative-multi-site


# ent

id: cord-269448-1jikrn37
type: DNA
entity:
  FML saponinvaccinated dogs 7 79 mm average skin test diameter 17 and in 82 7 of Leishmune vaccinated dogs


id: cord-279364-j93f6eso
type: ORG
entity:
  Programme Duration Vaccination Location Vaccination Arrangement Procedure Vaccination Service Hours and Proportion of Colleagues


id: cord-254620-xcblqg4z
type: ORG
entity:
  Veerle Mertens Belgian Superior Health Council Canada National Advisory Committee on Immunization NACI Togo Groupe


id: cord-254620-xcblqg4z
type: ORG
entity:
  National Conference of State Legislators States With Religious and Philosophical Exemptions From School Immunization Requirements Immunization


id: cord-288038-jdinf8od
type: ORG
entity:
  the Effectiveness and Efficacy of Pneumococcal Vaccination on Pneumonia and Invasive Pneumococcal Disease


id: cord-282764-d9x1wii6
type: PROTEIN
entity:
  SARS CoV S protein fragments residues 318 510 receptor binding domain 9 residues 485 625 10 and residues 803 828


id: cord-298551-ua90xoak
type: DISEASE
entity:
  respiratory viruses adenovirus bocavirus coronavirus enterovirus human metapneumovirus parainfluenza virus 1 3 and rhinovirus 5


id: cord-276907-b855tj7x
type: ORG
entity:
  A Sobanjo ter Meulen Advancing Maternal Immunization Programs through Research in Low and Medium Income Countries Global


id: cord-277355-si3g5dih
type: DNA
entity:
  CP coding sequence 35 2 The 5 0 downstream AUG region 5 0 DAR and 3 5 0 cyclization sequence 5 0 CS 36 37 38 4 A stable hairpin


id: cord-277355-si3g5dih
type: DNA
entity:
  C D51 87 1 0 PFU mouse 23 76 DENV C D41 49 C D42 51 ND b mouse 75 ZIKV C D63 71 prM E21K NS2B E27G 10 5 FFU mouse 33


id: cord-297022-zs5m36cp
type: CELL_LINE
entity:
  Toronto Mount Sinai Hospital Canada Douglas G Manuel Institute for Clinical Evaluative Sciences Canada


id: cord-276009-p98wjtjb
type: DNA
entity:
  5 and 3 using 5 WNE FLAG Not I 5 GACGACGCGGCCGC ATGTTTAACTGCCTTGGAA TGAGC 3 and 3 WNE FLAG BamHI 5 GCAGCAGGATCCAGCGTGCACGTTCACGG AGAGG 3 primers NotI


id: cord-276009-p98wjtjb
type: DNA
entity:
  5 XN2 Xho I 5 CCGCGGCTCGAGATGTTT AACTGCCTTGGAATGAGC 3 and 3 XN2 Nhe I 5 GACGACGCTAGCGGATCACTAC TTGTCATCGTC 3 primers XhoI


id: cord-296469-h0ma163u
type: ORG
entity:
  Influenza Vaccines Geneva World Health Organization Pandemic Influenza Preparedness PIP Framework Geneva World Health Organization


id: cord-283475-28900qlr
type: EVENT
entity:
  the Global Vaccine Action Plan Strategic Advisory Group of Experts on Immunization Geneva World Health Organization


id: cord-302222-9ad0fw6z
type: DISEASE
entity:
  meningitis encephalitis endocarditis glomerulonephritis osteomyelitis neuropsychiatric abnormalities


id: cord-307939-rydgncys
type: CELL_LINE
entity:
  Beijing China A Large Population Based Survey Multistage sampling A cross sectional study of pandemic influenza health literacy and the effect of a public health campaign Public perceptions and reactions to H7N9


id: cord-307939-rydgncys
type: DISEASE
entity:
  influenza A H7N9 China Food and Drug Administration Data Query Safety and immunogenicity of an inactivated cell culture derived H7N9 influenza vaccine


id: cord-267712-mhx8e5y0
type: DISEASE
entity:
  Influenza virus Ebola virus Marburg virus Human immunodeficiency HIV virus Severe Acute Respiratory Syndrome SARS virus and Hepatitis C virus 5 6 7 8 9


id: cord-299952-xvtt8fz8
type: ORG
entity:
  the third party National Institute for Viral Disease Control and Prevention China Center for Disease Control and Prevention of this


id: cord-299952-xvtt8fz8
type: DISEASE
entity:
  influenza virus parainfluenza virus respiratory syncytial virus rhinovirus adenovirus and coronavirus


id: cord-299952-xvtt8fz8
type: DISEASE
entity:
  influenza virus rhinovirus coronavirus and respiratory syncytial virus 10 11 12 13 14 However the major problem


id: cord-316295-x636ux34
type: TAXON
entity:
  adenovirus bocavirus coronavirus enterovirus metapneumovirus HMPV parainfluenza virus PIV rhinovirus


id: cord-316295-x636ux34
type: DISEASE
entity:
  adenovirus bocavirus coronavirus enterovirus metapneumovirus HMPV parainfluenza virus PIV rhinovirus and respiratory syncytial virus RSV


id: cord-316295-x636ux34
type: DISEASE
entity:
  influenza A H1N1 viruses cultivated in eggs or in canine kidney cell line MDCK Efficacy of inactivated influenza A virus H3N2


id: cord-281676-yy5etfek
type: CELL_TYPE
entity:
  natural killer NK cells CD3 CD4 CD8 40 T helper cells CD3 CD4 CD8 cytotoxic T lymphocytes CTLs CD3 CD4 CD8 CD4CD8 double positive T cells CD3 CD4 CD8


id: cord-281676-yy5etfek
type: CELL_TYPE
entity:
  T helper memory cells 41 42 T cells CD8 TcR1N4 T regulatory cells CD4 CD25 Foxp3 CD172 myeloid cells CD4 CD25 Foxp3 activated T helper cells dendritic cells


id: cord-292528-8kdhf123
type: DISEASE
entity:
  herpes simplex virus 2 37 cytomegalovirus 38 parainfluenza 39 West Nile virus 40 severe acute respiratory syndrome coronavirus SARs CoV


id: cord-268369-yj7m0n0f
type: CHEMICAL
entity:
  N linked oligosaccharide side chains About 5 6 kDa of oligosaccharide chains have high mannose content susceptible to Endo H and 6 9 kDa of oligosaccharide chains have low mannose residues resistant to Endo H To assess the number of N linked oligosaccharide chains the trypsin


id: cord-268369-yj7m0n0f
type: CHEMICAL
entity:
  N linked glycans in the endoplasmic reticulum Morphological and biochemical characterization of influenza


id: cord-316839-wckqscvm
type: CELL_LINE
entity:
  Herds B and C 166 and 162 calves respectively were enrolled and were eligible for inclusion in the study Table 1


id: cord-291510-jh2fdks4
type: CELL_LINE
entity:
  China 10 11 12 13 Severe nephritis false layer syndrome and high mortality are observed in chickens infected with this viral genotype


id: cord-291510-jh2fdks4
type: ORG
entity:
  the Animal Welfare Conceptualization Methodology Software Investigation Validation Visualization Resources Writing


id: cord-282158-08u3x1z4
type: ORG
entity:
  the Center for Biologics Evaluation and Research CBER and Committee for Medicinal Products for Human Use CHMP


id: cord-282158-08u3x1z4
type: DISEASE
entity:
  influenza A H1N1 pdm09 vaccines especially in terms of longterm immunogenicity There are conflicting reports on whether previous seasonal influenza vaccination increases the risk of subsequently contracting A H1N1 pdm09 infection


id: cord-282158-08u3x1z4
type: DISEASE
entity:
  influenza A H1N1 pdm09 vaccines 17 45 2 46 comparing safety outcomes between adjuvanted and non adjuvanted vaccines reported similar observations with higher frequency of both local and general adverse events with adjuvanted vaccines compared with non adjuvanted vaccines In our study we did not observe any differences between the two vaccine groups in terms of SAEs


id: cord-282158-08u3x1z4
type: DISEASE
entity:
  influenza A H1N1 pdm09 vaccines elicited protective levels of HI antibodies against the vaccine homologous A California 7 2009 strain that persisted up to Day 182 Month 6 in the 18 64 years population Adjuvantation potentially offers the opportunity for antigen sparing making this AS03 adjuvanted influenza A H1N1 pdm09 vaccine


id: cord-282158-08u3x1z4
type: DISEASE
entity:
  influenza A H1N1 virus after vaccination with seasonal influenza vaccine Cross reactive antibody responses to the 2009 pandemic


id: cord-263443-m98qisld
type: ORG
entity:
  Investigation Resources Writing Review Editing Investigation Resources Writing Review Editing 554 Samina Ali


id: cord-294856-eeh2a0t8
type: CELL_LINE
entity:
  China COVID 19 Data Center Developing Covid 19 Vaccines at Pandemic Speed Respiratory syncytial virus disease in infants despite prior administration of antigenic inactivated vaccine A


id: cord-294856-eeh2a0t8
type: CHEMICAL
entity:
  Samantha D Molrine Deborah C Perlman Stanley Picard Fraser Philip A Pollard Andrew J Qin Chuan Subbarao Kanta Cramer Jakob P title


id: cord-279985-de0b27nq
type: DISEASE
entity:
  human immunodeficiency virus vaccine development Kunjin virus replicons an RNA based non cytopathic viral vector system


id: cord-294789-07hto8qn
type: ORG
entity:
  human papillomavirus vaccination Trump Administration Announces Framework and Leadership for Operation


id: cord-255026-fdp6mies
type: ORG
entity:
  the Application of Polymerase Chain Reaction Methods for Diagnosis of Viral Diseases in Veterinary Medicine


id: cord-255026-fdp6mies
type: ORG
entity:
  the Application of Polymerase Chain Reaction Methods for the Diagnosis of Viral Diseases in Veterinary Medicine Genetic


id: cord-277054-eq4obbte
type: DISEASE
entity:
  HIV type 1 uninfected adults Phase I clinical trial safety of DNA and modified virus Ankara vectored human immunodeficiency virus type 1 HIV 1 vaccines administered alone


id: cord-270910-xb746mv5
type: DNA
entity:
  Northeast aPRR 0 74 95 CI 0 54 0 93 CONCLUSIONS Influenza vaccination coverage among pediatric health center patients


id: cord-270910-xb746mv5
type: ORG
entity:
  the National Health Interview Survey National Ambulatory Medical Care Survey Medical Expenditure Panel Survey


id: cord-270910-xb746mv5
type: ORG
entity:
  School Year Department of Health and Human Services Office of Disease Prevention and Health Promotion


id: cord-270910-xb746mv5
type: ORG
entity:
  Centers for Disease Control and Prevention National Center for Immunization and Respiratory Diseases Children


id: cord-270910-xb746mv5
type: ORG
entity:
  Flu Vaccination Campaign Department of Health and Human Services Office of Disease Prevention and Health Promotion


id: cord-270910-xb746mv5
type: ORG
entity:
  Improve Access To Care Preventive Services And Satisfaction Among Health Center Patients Organizational Factors Associated with Disparities in Cervical and


id: cord-270910-xb746mv5
type: ORG
entity:
  Health Resources and Services Administration Bureau of Primary Health Care Primary Care Associations Health Resources and Services Administration Bureau of Primary Health Care Racial


id: cord-271734-1cfhjuxi
type: PROTEIN
entity:
  anti guinea pig cell monoclonal antibodies 37 40 MSgp7 pan T marker antibodies CT6 putative T suppressor cell marker antibodies


id: cord-315437-h6xjudm0
type: CELL_LINE
entity:
  Huh 7 cell lysates 5 Â 10 7 mL in 1 mL lysis buffer containing 0 3 N decyl D maltopyranoside phosphate


id: cord-315437-h6xjudm0
type: PROTEIN
entity:
  Ron A Fouchier Erasmus Medical Center Rotterdam The Netherlands followed by daily monitoring for the onset of clinical manifestations e g weight


id: cord-299323-riotkgj4
type: ORG
entity:
  the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use ICH


id: cord-299323-riotkgj4
type: ORG
entity:
  The International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use History ICH Quality Guidelines An Implementation Guide Priority


id: cord-299323-riotkgj4
type: ORG
entity:
  The International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use M4


id: cord-271076-436nxsua
type: ORG
entity:
  the international committee on taxonomy of viruses Virology Division International Union of Microbiological Societies Viral metagenomics


id: cord-252293-8286lsof
type: DISEASE
entity:
  diabetes mellitus heart failure ischemic heart disease cerebrovascular disease liver disease renal disease neurological disease cancer chronic obstructive pulmonary disease bronchial asthma


id: cord-294302-hboc3xcz
type: CELL_TYPE
entity:
  natural killers NK and dendritic cells activator 50 51 52 In 1985 Cioffi and colleagues reported that C parvum protects splenectomized Sprague Dawley rats


id: cord-260761-ngms51ie
type: DISEASE
entity:
  Respiratory syncytial virus RSV evades the human adaptive immune system by skewing the Th1 Th2 cytokine balance


id: cord-260761-ngms51ie
type: DISEASE
entity:
  chimpanzees of vaccinia virus recombinants that express the surface glycoproteins of human respiratory syncytial virus Leucine


id: cord-325998-87l6nixc
type: CHEMICAL
entity:
  Karpoff N Dai X Das D Sun L Q Wang M Salazar A M title Activation of toll like receptor signaling pathway


id: cord-325998-87l6nixc
type: CHEMICAL
entity:
  alpha interferon in respiratory syncytial virus and human metapneumovirus experimental infections Toll like receptor


id: cord-340686-uq0fsqh3
type: CELL_TYPE
entity:
  follows NK cells CD3 CD4 CD8 42 T helper cells CD3 CD4 CD8 cytotoxic T lymphocytes CTLs CD3 CD4 CD8 T cells CD8 TcR1N4 T regulatory cells CD4 CD25 FOXP3 myeloid cells


id: cord-340686-uq0fsqh3
type: DISEASE
entity:
  influenza parainfluenza respiratory syncytial virus rotavirus and HIV SIV 26 29 48 49 Consistent with a high degree of compartmentalization the mucosal immune system


id: cord-303200-hwvkvdlk
type: DNA
entity:
  mammalian reoviruses MRV 19 20 rotaviruses 21 caliciviruses 22 23 canine adenoviruses 24 canine distemper virus CDV 25 canine herpesvirus 26 and canine coronavirus CCoV 27 28 Specimens


id: cord-341626-04svm6le
type: DISEASE
entity:
  influenza and respiratory syncytial virus Respiratory syncytial virus or influenza Respiratory syncytial virus infection


id: cord-341626-04svm6le
type: DISEASE
entity:
  influenza and respiratory syncytial virus active periods Influenza and respiratory syncytial virus morbidity


id: cord-341626-04svm6le
type: DISEASE
entity:
  influenza and respiratory syncytial virus in the United States Contribution of respiratory syncytial virus influenza and parainfluenza viruses to acute respiratory infections


# url

id: cord-324911-6s7ubbxl
domain: wellcome.ac.uk
url:
  http://wellcome.ac.uk/press-release/unprecedented-international-consortiumassembled-accelerate-collaborative-multi-site


# bib

id: cord-007440-7gcpk9x9
title: Vaccines and sera through plant biotechnology()
author: Koprowski, Hilary
date: 2005-03-07
txt: ./txt/cord-007440-7gcpk9x9.txt
cache: ./cache/cord-007440-7gcpk9x9.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7115416/
doi: 10.1016/j.vaccine.2004.11.001
abstract: nan
summary:
  After considering various alternatives of fulfilling the criteria established for a global approach to immunization, it has become clear that our only choice is the production of vaccines or other materials of biomedical importance in plants. Immunogenicity was tested in mice, which were either injected with or fed the plant-produced vaccine ( as compared to controls; high-titer antibodies against RSV were also induced. To express rabies vaccine in plants, we have used a recombinant alfalfa mosaic virus in spinach leaves. Research conducted by Dr. Kisung Ko, led to the production of a transgenic tobacco plant containing the heavy and light chains of human rabies antibody. The two chains recombined in the plants to produce a complete antirabies antibody, which was as effective as the original antibody in animals, before and after exposure to rabies (Table 4 ).


id: cord-010266-elhgew3x
title: Ethical aspects of vaccines and vaccination
author: Spier, R.E.
date: 1998-12-02
txt: ./txt/cord-010266-elhgew3x.txt
cache: ./cache/cord-010266-elhgew3x.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7173252/
doi: 10.1016/s0264-410x(98)00169-8
abstract: nan
summary:
  An example of the implications of these changes may be seen in the area of vaccines and vaccination which evinces the pressing need to review traditional ethical positions to take the maximum advantage of the potential for animal and human benefit inherent in this prophylactic approach to healthcare. Such an ethical problem is thrown up by the willingness of our communities to spend billions of dollars to provide therapeutic and prophylactic agents to control the spread and effects of the Human Immunodeficiency Virus (HIV), while the disease would be eliminated were people to engage in safe, condom-protected, intercourse in their pre-or extramarital sexual relationships where the prospective partners had not been thoroughly tested for the presence of serum antibodies to the virus. Were we to have an effective orally deliverable contraceptive vaccine'' (pregnancy results from the infection of the female by a male spermatozoan) then ethical considerations will be required to determine the way in which such a powerful tool for population control might be used.


id: cord-010279-ytnv0map
author: Bahnemann, Hans G.
date: 2002-11-12
txt: ./txt/cord-010279-ytnv0map.txt
cache: ./cache/cord-010279-ytnv0map.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7173316/
doi: 10.1016/0264-410x(90)90083-x
summary:
  The preparation and application of the aziridine compound binary ethylenimine (BEI) and the necessary conditions for and controls of the inactivation process are described and discussed. The first report of a (bacterial) virus inactivation by ethylenimine, the basic aziridine substance, was published in 1955 by Raettig and Uecker Is. Hurst in 1957 x6 was of the opinion that vaccines prepared with AEI as inactivant were antigenically superior to vaccines inactivated with formaldehyde and would guarantee inactivation of the virus. In 1961 Uecker 22 reported the linearity of inactivation of bacterial viruses by ethylenimine derivatives and Graves and Arlinghaus described in 1967 the linearity of AEI inactivation of foot-and-mouth disease virus 23. Formaldehyde inactivation of foot-and-mouth disease virus as applied to vaccine preparation Binary ethylenimine as an inactivant for foot-and-mouth disease virus and its application for vaccine production

title:
  Inactivation of viral antigens for vaccine preparation with particular reference to the application of binary ethylenimine

abstract:
  Viral antigens for human and veterinary vaccines are still inactivated with formaldehyde. This is not an ideal inactivant and the problems of formaldehyde inactivation of vaccines are discussed. Vaccines inactivated with aziridines are superior in safety and antigenicity. Aziridines inactivate viruses in a first-order reaction and the inactivation rate and endpoint can be determined. The preparation and application of the aziridine compound binary ethylenimine (BEI) and the necessary conditions for and controls of the inactivation process are described and discussed. A computer program has been written for assistance in the use of BEI for controlled inactivation of viral antigens.


id: cord-252293-8286lsof
author: Suzuki, Motoi
date: 2018-05-17
url: https://doi.org/10.1016/j.vaccine.2018.04.037
doi: 10.1016/j.vaccine.2018.04.037
title:
  Effectiveness of inactivated influenza vaccine against laboratory-confirmed influenza pneumonia among adults aged ≥65 years in Japan

abstract:
  BACKGROUND: The effectiveness of inactivated influenza vaccine (IIV) against laboratory-confirmed influenza pneumonia in older adults remains to be established. METHODS: Pneumonia patients aged ≥65 years who visited a study hospital in Chiba, Japan, were prospectively enrolled from February 2012 to January 2014. Sputum samples were collected from participants and tested for influenza virus by polymerase chain reaction assays. Influenza vaccine effectiveness (IVE) against laboratory-confirmed influenza pneumonia was estimated by a test-negative design. RESULTS: Among a total of 814 pneumonia patients, 42 (5.2%) tested positive for influenza: 40 were positive for influenza A virus, and two were positive for influenza B virus. The IVE against laboratory-confirmed influenza pneumonia was 58.3% (95% confidence interval, 28.8–75.6%). The IVE against influenza pneumonia hospital admission, severe pneumonia, and death was 60.2% (95% CI, 22.8–79.4%), 65.5% (95% CI, 44.3–78.7%), and 71% (95% CI, −62.9% to 94.8%), respectively. In the subgroup analyses, the IVE against influenza pneumonia was higher for patients with immunosuppressive conditions (85.9%; 95% CI, 67.4–93.9%) than for those without (48.7%; 95% CI, 2.7–73%) but did not differ by patients’ statin use status. CONCLUSION: IIV effectively reduces the risk of laboratory-confirmed influenza pneumonia in older adults.


id: cord-252856-oc0zd11h
author: Pagliusi, Sonia
date: 2016-06-30
txt: ./txt/cord-252856-oc0zd11h.txt
cache: ./cache/cord-252856-oc0zd11h.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1016/j.vaccine.2016.02.067
doi: 10.1016/j.vaccine.2016.02.067
summary:
  The Developing Countries Vaccine Manufacturers Network (DCVMN) assembled high-profile leaders from global health organisations and vaccine manufactures for its 16th Annual General Meeting to work towards a common goal: providing quality vaccines for all people. DCVMN members presented their progress in developing novel vaccines against Dengue, HPV, Chikungunya, Cholera, cell-based influenza and other vaccines, demonstrating the commitment towards eliminating and eradicating preventable diseases worldwide through global collaboration and technology transfer. Combatting preventable diseases remains challenging, and collective efforts for improving multi-centre clinical trials, creating regional vaccine security strategies, fostering developing vaccine markets and procurement, and building trust in vaccines were discussed. DCVMN is the largest alliance of corporate manufacturers, supplying over 300 vaccine types in various presentations to immunisation programmes, and contributing significantly to global public health efforts to eradicate polio, eliminate and control the spread of known and emerging infectious diseases around the world.

title:
  Quality vaccines for all people(): Report on the 16th annual general meeting of the Developing Countries Vaccine Manufacturers'' Network, 05–07th October 2015, Bangkok, Thailand

abstract:
  The Developing Countries Vaccine Manufacturers Network (DCVMN) assembled high-profile leaders from global health organisations and vaccine manufactures for its 16th Annual General Meeting to work towards a common goal: providing quality vaccines for all people. Vaccines contribute to a healthy community and robust health system; the Ebola outbreak has raised awareness of the threat and damage one single infectious disease can make, and it is clear that the world was not prepared. However, more research to better understand emerging infectious agents might lead to suitable vaccines which help prevent future outbreaks. DCVMN members presented their progress in developing novel vaccines against Dengue, HPV, Chikungunya, Cholera, cell-based influenza and other vaccines, demonstrating the commitment towards eliminating and eradicating preventable diseases worldwide through global collaboration and technology transfer. The successful introduction of novel Sabin-IPV and Oral Cholera vaccine in China and Korea respectively in 2015 was highlighted. In order to achieve global immunisation, local authorities and community leaders play an important role in the decision-making in vaccine introduction and uptake, based on the ability of vaccines to protect vaccinated people and protect non-vaccinated in the community through herd immunity. Reducing the risk of vaccine shortages can also be achieved by increasing regulatory convergence at regional and international levels. Combatting preventable diseases remains challenging, and collective efforts for improving multi-centre clinical trials, creating regional vaccine security strategies, fostering developing vaccine markets and procurement, and building trust in vaccines were discussed.


id: cord-253477-gptjqti7
author: Ball, Christopher
date: 2019-12-10
txt: ./txt/cord-253477-gptjqti7.txt
cache: ./cache/cord-253477-gptjqti7.txt
extension: .txt
mime: text/plain
url: https://www.sciencedirect.com/science/article/pii/S0264410X19313234
doi: 10.1016/j.vaccine.2019.09.081
summary:
  title: Comparative protective immunity provided by live vaccines of Newcastle disease virus or avian metapneumovirus when co-administered alongside classical and variant strains of infectious bronchitis virus in day-old broiler chicks Abstract This study reports on the simultaneous administration of live NDV or aMPV subtype B vaccines alongside two live IBV (Massachusetts-H120 and 793B-CR88) vaccines in day-old maternal-antibody positive commercial broiler chicks. Infectious bronchitis virus (IBV), avian metapneumovirus (aMPV) and Newcastle Disease virus (NDV) are respiratory RNA viruses that primarily infect the tracheal epithelium of chickens [7] . Post challenge, high viral loads were present in the trachea (Fig. 2 For the kidney samples at 14 and 21 dpv, Groups B (IBV vaccinated) and C (NDV + IBV vaccinated) increased from 14 to 21 dpv (0.81 to 3.13 log REU and 1.15 to 1.42 log REU respectively) (Fig. 1) .

title:
  Comparative protective immunity provided by live vaccines of Newcastle disease virus or avian metapneumovirus when co-administered alongside classical and variant strains of infectious bronchitis virus in day-old broiler chicks

abstract:
  Abstract This study reports on the simultaneous administration of live NDV or aMPV subtype B vaccines alongside two live IBV (Massachusetts-H120 and 793B-CR88) vaccines in day-old maternal-antibody positive commercial broiler chicks. In the first experiment, chicks were divided into four groups; one unvaccinated and three groups vaccinated with live NDV VG/GA-Avinew, live H120 + CR88, or VG/GA-Avinew + H120 + CR88. In the second experiment, live aMPV subtype B vaccine was used in place of NDV. Clinical signs were monitored daily and oropharyngeal swabs were taken at regular intervals for vaccine virus detection. Blood was collected at 21 dpv for serology. 10 chicks from each group were challenged with virulent strains of M41 or QX or aMPV subtype B. For IBV, after 5 days post challenge (dpc), tracheal ciliary protection was assessed. For aMPV, clinical scores were recorded up to 10 dpc. For NDV, haemagglutination inhibition (HI) antibody titres were assayed as an indicator of protective immunity. In both experiments, ciliary protection for IBV vaccinated groups was maintained above 90%. The protection against virulent aMPV challenge was not compromised when aMPV, H120 and CR88 were co-administered. NDV HI mean titres in single and combined NDV-vaccinated groups remained above the protective titre (>3 log2). Both experiments demonstrated that simultaneous administration of live NDV VG/GA-Avinew or aMPV subtype B alongside H120 and CR88 vaccines does not interfere with protection conferred against NDV, IBV or aMPV.


id: cord-253656-2x4y403o
author: Ren, Wenlin
date: 2020-06-24
txt: ./txt/cord-253656-2x4y403o.txt
cache: ./cache/cord-253656-2x4y403o.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/32651113/
doi: 10.1016/j.vaccine.2020.06.066
summary:
  In this study, we examined the immunogenicity of CHO-expressed recombinant SARS-CoV-2 S1-Fc fusion protein in mice, rabbits, and monkeys as a potential candidate for a COVID-19 vaccine. Most importantly, in less than 20 days and three injections of the S1-Fc fusion protein, two monkeys developed higher virus neutralizing titers than a recovered COVID-19 patient in a live SARS-CoV-2 infection assay. The sera were collected on Day 38 and evaluated by ELISA against SARS-CoV-2 S1-6His protein using HRP-conjugated goat anti-mouse IgG Fc-specific secondary antibodies. As shown in Table 1 and Fig. 5A , immunization of SARS-CoV-2 S1-Fc fusion protein with AD20Gold + as adjuvant also induced very high neutralizing activities with IC50 titers >3000 and IC90 titers around 440-501 in both rabbits on Day 27 after immunizations. Beside high levels of the anti-S1 antibodies elicited, higher neutralizing activities against live SARS-CoV-2 virus and/or pseudovirus from the anti-sera of macaques and rabbits.

title:
  Recombinant SARS-CoV-2 spike S1-Fc fusion protein induced high levels of neutralizing responses in nonhuman primates

abstract:
  Abstract The COVID-19 outbreak has become a global pandemic responsible for over 2,000,000 confirmed cases and over 126,000 deaths worldwide. In this study, we examined the immunogenicity of CHO-expressed recombinant SARS-CoV-2 S1-Fc fusion protein in mice, rabbits, and monkeys as a potential candidate for a COVID-19 vaccine. We demonstrate that the S1-Fc fusion protein is extremely immunogenic, as evidenced by strong antibody titers observed by day 7. Strong virus neutralizing activity was observed on day 14 in rabbits immunized with the S1-Fc fusion protein using a pseudovirus neutralization assay. Most importantly, in less than 20 days and three injections of the S1-Fc fusion protein, two monkeys developed higher virus neutralizing titers than a recovered COVID-19 patient in a live SARS-CoV-2 infection assay. Our data strongly suggests that the CHO-expressed SARS-CoV-2 S1-Fc recombinant protein could be a strong candidate for vaccine development against COVID-19.


id: cord-254620-xcblqg4z
title: Immunization governance: Mandatory immunization in 28 Global NITAG Network countries()
author: Harmon, Shawn H.E.
date: 2020-09-26
txt: ./txt/cord-254620-xcblqg4z.txt
cache: ./cache/cord-254620-xcblqg4z.txt
extension: .txt
mime: text/plain
url: https://www.sciencedirect.com/science/article/pii/S0264410X20312238
doi: 10.1016/j.vaccine.2020.09.053
summary:
  More detailed empirical case studies would be necessary to uncover the policy reasons for the presence or absence of mandates within NIPs. Nonetheless, it may be reasonable to infer that lower-income countries have fewer human and financial resources to undertake, administer, and enforce mandayWe were unable to verify the legal basis for mandatory immunization in Jordan. Survey participants in countries with mandatory immunization were asked about specific populations subject to mandates (i.e., age [children under 1 and 5 years of age and school-aged children -that yExcludes Canada and the USA due to subnational variation in those countries. However, it should be noted that these subnational jurisdictions appear also to have relatively broad mandates -Ontario and New Brunswick require immunization against 9 and 11 infectious diseases, respectively, for school entry, with similarthough varying -numbers for US states.

abstract:
  International trends currently favour greater use of mandatory immunization. There has been little academic consideration or comparison of the existence and scope of mandatory immunization internationally. In this paper, we examine mandatory immunization in 28 Global NITAG (National Immunization Technical Advisory Group) Network (GNN) countries, including countries from every WHO region and World Bank income level classification. We found that although mandatory immunization programs, or mandatory elements within broader immunization programs, are relatively common, jurisdictions vary significantly with respect to the immunizations required, population groups affected, grounds for exemptions, and penalties for non-compliance. We also observed some loose associations with geography and income level. Based on these data, we categorized policies into a spectrum ranging from Narrow to Broad scope.


id: cord-255026-fdp6mies
author: Belák, Sándor
date: 2007-07-26
txt: ./txt/cord-255026-fdp6mies.txt
cache: ./cache/cord-255026-fdp6mies.txt
extension: .txt
mime: text/plain
url: https://www.sciencedirect.com/science/article/pii/S0264410X06012989
doi: 10.1016/j.vaccine.2006.11.068
summary:
  The experiences of an OIE-Collaborating Centre and of two EU project consortia are summarised on the diagnostic application of gel-based PCR, general PCR systems, phylogeny, molecular epidemiology, real-time PCR (TaqMan, Molecular Beacons, Primer-Probe Energy Transfer), amplification without thermocycling (Invader), multiplex PCR, nucleic acid extraction and pipetting robotics, automation and quality control, including internal controls.

title:
  Molecular diagnosis of viral diseases, present trends and future aspects: A view from the OIE Collaborating Centre for the Application of Polymerase Chain Reaction Methods for Diagnosis of Viral Diseases in Veterinary Medicine

abstract:
  The emergence and re-emergence of transboundary animal diseases (TADs), e.g., foot-and-mouth disease, classical swine fever and the highly pathogenic avian influenza strongly indicate the need for the development of powerful and robust new diagnostic methods. The experiences of an OIE-Collaborating Centre and of two EU project consortia are summarised on the diagnostic application of gel-based PCR, general PCR systems, phylogeny, molecular epidemiology, real-time PCR (TaqMan, Molecular Beacons, Primer-Probe Energy Transfer), amplification without thermocycling (Invader), multiplex PCR, nucleic acid extraction and pipetting robotics, automation and quality control, including internal controls. By following the steps of OIE validation, the diagnostic assays are nationally and internationally standardised. The development of padlock probes and microarrays, as well as ultra rapid PCR and sequencing methods is further improving the arsenal of nucleic acid based molecular diagnosis. Further trends of diagnostic development are also mentioned, in order to combat TADs and other viral infections more effectively in the future.


id: cord-255549-i2o6rs29
title: Vaccines: Shaping global health()
author: Pagliusi, Sonia
date: 2017-03-14
txt: ./txt/cord-255549-i2o6rs29.txt
cache: ./cache/cord-255549-i2o6rs29.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/28237501/
doi: 10.1016/j.vaccine.2017.02.017
summary:
  After decades of intense competition for high-value markets, collaboration with developing countries has become critical, and involvement of multiple manufacturers as well as publicand private-sector investments are essential, for developing new vaccines against emerging infectious diseases. Face-to-face panel discussions facilitated the dialogue around challenges, such as risks of viability to vaccine development and regulatory convergence, to improve access to sustainable vaccine supply. In 2016, 50 corporate members are working to provide high-quality vaccines, and contribute to global health initiatives, ensuring uninterrupted vaccine supply to countries, to advance eradication of polio and facilitate response to emerging infectious diseases (EIDs) or outbreaks like the Zika outbreak [1] . I. Danel, Deputy Director from PAHO, outlined achievements of public health goals in the Americas, including extension of the reach of national immunization programs, new vaccine introductions, strengthening of regulatory pathways and improving financing and forecasting mechanisms.

abstract:
  The Developing Countries Vaccine Manufacturers’ Network (DCVMN) gathered leaders in immunization programs, vaccine manufacturing, representatives of the Argentinean Health Authorities and Pan American Health Organization, among other global health stakeholders, for its 17th Annual General Meeting in Buenos Aires, to reflect on how vaccines are shaping global health. Polio eradication and elimination of measles and rubella from the Americas is a result of successful collaboration, made possible by timely supply of affordable vaccines. After decades of intense competition for high-value markets, collaboration with developing countries has become critical, and involvement of multiple manufacturers as well as public- and private-sector investments are essential, for developing new vaccines against emerging infectious diseases. The recent Zika virus outbreak and the accelerated Ebola vaccine development exemplify the need for international partnerships to combat infectious diseases. A new player, Coalition for Epidemic Preparedness Innovations (CEPI) has made its entrance in the global health community, aiming to stimulate research preparedness against emerging infections. Face-to-face panel discussions facilitated the dialogue around challenges, such as risks of viability to vaccine development and regulatory convergence, to improve access to sustainable vaccine supply. It was discussed that joint efforts to optimizing regulatory pathways in developing countries, reducing registration time by up to 50%, are required. Outbreaks of emerging infections and the global Polio eradication and containment challenges are reminders of the importance of vaccines’ access, and of the importance of new public-private partnerships.


id: cord-255734-038xu4hq
title: Obstacles and advances in SARS vaccine development
author: Taylor, Deborah R.
date: 2006-02-13
txt: ./txt/cord-255734-038xu4hq.txt
cache: ./cache/cord-255734-038xu4hq.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/16191455/
doi: 10.1016/j.vaccine.2005.08.102
summary:
  The emergence of the severe acute respiratory syndrome (SARS) that resulted in a pandemic in 2003 spurred a flurry of interest in the development of vaccines to prevent and treat the potentially deadly viral infection. Spike-specific monoclonal and polyclonal antibodies that neutralize the virus have been developed [51, 52] and passive transfer of immune serum into naive mice protected them from infection with SARS-CoV [18] . Mice immunized with a plasmid containing the S protein produced anti-SARS-CoV IgG [64] and developed neutralizing antibodies and a T-cell mediated response resulting in a six-fold reduction in viral titer in the lungs [65] . Inactivation of the coronavirus that induces severe acute respiratory syndrome, SARS-CoV Severe acute respiratory syndrome coronavirus spike protein expressed by attenuated vaccinia virus protectively immunizes mice Immunization with modified vaccinia virus Ankara-based recombinant vaccine against severe acute respiratory syndrome is associated with enhanced hepatitis in ferrets

abstract:
  The emergence of the severe acute respiratory syndrome (SARS) that resulted in a pandemic in 2003 spurred a flurry of interest in the development of vaccines to prevent and treat the potentially deadly viral infection. Researchers around the world pooled their scientific resources and shared early data in an unprecedented manner in light of the impending public health crisis. There are still large gaps in knowledge about the pathogenesis of this virus. While significant advances have been made in the development of animal models, the practicality of their use may be hampered by a lack of pathological similarity with human disease. Described here are issues related to progress in vaccine development and the obstacles that lie ahead for both researchers and regulatory agencies.


id: cord-256784-wfaqim7d
title: MERS-CoV vaccine candidates in development: The current landscape
author: Modjarrad, Kayvon
date: 2016-06-03
txt: ./txt/cord-256784-wfaqim7d.txt
cache: ./cache/cord-256784-wfaqim7d.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/27083424/
doi: 10.1016/j.vaccine.2016.03.104
summary:
  Middle East Respiratory Syndrome (MERS-CoV) was first isolated in September 2012 from a patient in Saudi Arabia who presented two months earlier with severe acute respiratory infection and acute renal failure [1] . Middle East respiratory syndrome coronavirus infection in dromedary camels in Saudi Arabia A truncated receptor-binding domain of MERS-CoV spike protein potently inhibits MERS-CoV infection and induces strong neutralizing antibody responses: implication for developing therapeutics and vaccines Effects of human anti-spike protein receptor binding domain antibodies on severe acute respiratory syndrome coronavirus neutralization escape and fitness Middle East respiratory syndrome coronavirus spike protein delivered by modified vaccinia virus Ankara efficiently induces virus-neutralizing antibodies Systemic and mucosal immunity in mice elicited by a single immunization with human adenovirus type 5 or 41 vector-based vaccines carrying the spike protein of Middle East respiratory syndrome coronavirus Exceptionally potent neutralization of Middle East respiratory syndrome coronavirus by human monoclonal antibodies

abstract:
  Middle East respiratory syndrome coronavirus (MERS-CoV), an emerging infectious disease of growing global importance, has caused severe acute respiratory disease in more than 1600 people, resulting in more than 600 deaths. The high case fatality rate, growing geographic distribution and vaguely defined epidemiology of MERS-CoV have created an urgent need for effective public health countermeasures, paramount of which is an effective means of prevention through a vaccine or antibody prophylaxis. Despite the relatively few number of cases to-date, research and development of MERS-CoV vaccine candidates is advancing quickly. This review surveys the landscape of these efforts across multiple groups in academia, government and industry.


id: cord-257533-i85dyg8n
author: Henn, Wolfram
date: 2020-06-23
txt: ./txt/cord-257533-i85dyg8n.txt
cache: ./cache/cord-257533-i85dyg8n.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/32600909/
doi: 10.1016/j.vaccine.2020.06.058
abstract: nan
summary:
  title: Allocation criteria for an initial shortage of a future SARS-CoV-2 vaccine and necessary measures for global immunity Although healthcare systems around the world currently are fully absorbed with the day-today challenge of slowing down the spread of the SARS-CoV-2 virus, ongoing research makes it very likely that a protective vaccine will be developed within a rather short period of time [1, 2] . Given the unprecedented public attention to the issue, these criteria must be medically adequate, socially fair, transparent, verifiable, and easily understandable for non-experts, in order to bridge thehopefully short but anyway relevant-initial shortage of vaccine supply without creating social discomfort or even unrest. As current data clearly show that COVID-19 mortality is strongly associated with age [7] , it should be the leading and also easily verifiable medical parameter for the distribution of the expected vaccine during an initial scarcity.

title:
  Allocation criteria for an initial shortage of a future SARS-CoV-2 vaccine and necessary measures for global immunity


id: cord-257792-m7nij17v
title: Memory T cell responses targeting the SARS coronavirus persist up to 11 years post-infection
author: Ng, Oi-Wing
date: 2016-04-12
txt: ./txt/cord-257792-m7nij17v.txt
cache: ./cache/cord-257792-m7nij17v.txt
extension: .txt
mime: text/plain
url: https://api.elsevier.com/content/article/pii/S0264410X16002589
doi: 10.1016/j.vaccine.2016.02.063
summary:
  In this study, the screening for the presence of SARS-specific T cells in a cohort of three SARS-recovered individuals at 9 and 11 years post-infection was carried out, and all memory T cell responses detected target the SARS-CoV structural proteins. As shown in Fig. 1 , higher frequencies of IFN␥producing SFUs were observed for in vitro-expanded PBMCs from SARS subject 1 compared to the healthy individual, suggesting the presence of SARS-specific memory T cells at 9 years post-infection. In another study looking at SARSspecific memory T cell responses in SARS-recovered individuals at 4 years post-infection, 28.75% of them presented T cell responses to M peptides [22] , further supporting the role of M protein in eliciting dominant cellular immunity during SARS-CoV infection. In SARS subject 1 at 6 years post-infection, a HLA-B*1525-restricted memory CD8 + T cell response targeting the N53 peptide, corresponding to residues 261-275 of N protein, was detected.

abstract:
  Severe acute respiratory syndrome (SARS) is a highly contagious infectious disease which first emerged in late 2002, caused by a then novel human coronavirus, SARS coronavirus (SARS-CoV). The virus is believed to have originated from bats and transmitted to human through intermediate animals such as civet cats. The re-emergence of SARS-CoV remains a valid concern due to the continual persistence of zoonotic SARS-CoVs and SARS-like CoVs (SL-CoVs) in bat reservoirs. In this study, the screening for the presence of SARS-specific T cells in a cohort of three SARS-recovered individuals at 9 and 11 years post-infection was carried out, and all memory T cell responses detected target the SARS-CoV structural proteins. Two CD8(+) T cell responses targeting the SARS-CoV membrane (M) and nucleocapsid (N) proteins were characterized by determining their HLA restriction and minimal T cell epitope regions. Furthermore, these responses were found to persist up to 11 years post-infection. An absence of cross-reactivity of these CD8(+) T cell responses against the newly-emerged Middle East respiratory syndrome coronavirus (MERS-CoV) was also demonstrated. The knowledge of the persistence of SARS-specific celullar immunity targeting the viral structural proteins in SARS-recovered individuals is important in the design and development of SARS vaccines, which are currently unavailable.


id: cord-258902-h0wrs01h
author: Liu, Xianglei
date: 2020-09-22
txt: ./txt/cord-258902-h0wrs01h.txt
cache: ./cache/cord-258902-h0wrs01h.txt
extension: .txt
mime: text/plain
url: https://www.sciencedirect.com/science/article/pii/S0264410X20312299?v=s5
doi: 10.1016/j.vaccine.2020.09.058
summary:
  title: Enhanced Elicitation of Potent Neutralizing Antibodies by the SARS-CoV-2 Spike Receptor Binding Domain Fc Fusion Protein in Mice The cell-cell fusion assay results correlated well with the virus neutralization potency and could be used for high-throughput screening of large panels of anti-SARS-CoV-2 antibodies and vaccines without the requirement of live virus infection in BSL3 containment. Based on its highly homology to SARS-CoV, SARS-CoV-2 RBD is corroborated to contain immune dominant epitopes capable of eliciting antibodies that can neutralize viral infection and block viral entry by competing hACE2 Pseudovirus neutralization assay was then performed by incubation of SARS-CoV-2 pseudovirus with serially diluted mice serum for 1h at 37 °C, followed by addition of the mixture into pre-seeded 293T-ACE2 cells. On day 0 (pre-immunization), day 13 and day 27, mouse sera were collected and analyzed for RBD binding, pseudovirus and live virus neutralization, and cell-cell fusion inhibition.

title:
  Enhanced Elicitation of Potent Neutralizing Antibodies by the SARS-CoV-2 Spike Receptor Binding Domain Fc Fusion Protein in Mice

abstract:
  The development of an effective vaccine against SARS-CoV-2 is urgently needed. We generated SARS-CoV-2 RBD-Fc fusion protein and evaluated its potency to elicit neutralizing antibody response in mice. RBD-Fc elicited a higher neutralizing antibodies titer than RBD as evaluated by a pseudovirus neutralization assay and a live virus based microneutralization assay. Furthermore, RBD-Fc immunized sera better inhibited cell-cell fusion, as evaluated by a quantitative cell-cell fusion assay. The cell-cell fusion assay results correlated well with the virus neutralization potency and could be used for high-throughput screening of large panels of anti-SARS-CoV-2 antibodies and vaccines without the requirement of live virus infection in BSL3 containment. Moreover, the anti-RBD sera did not enhance the pseudotyped SARS-CoV-2 infection of K562 cells. These results demonstrate that Fc fusion can significantly improve the humoral immune response to recombinant RBD immunogen, and suggest that RBD-Fc could serve as a useful component of effective vaccines against SARS-CoV-2.


id: cord-259299-z3o4t7mz
author: Chinsangaram, Jarasvech
date: 1998-10-31
txt: ./txt/cord-259299-z3o4t7mz.txt
cache: ./cache/cord-259299-z3o4t7mz.txt
extension: .txt
mime: text/plain
url: https://api.elsevier.com/content/article/pii/S0264410X98000292
doi: 10.1016/s0264-410x(98)00029-2
summary:
  title: Protection of swine by live and inactivated vaccines prepared from a leader proteinase-deficient serotype A12 foot-and-mouth disease virus Abstract Previously, we demonstrated that a genetically engineered variant of foot-and-mouth disease virus (FMDV) serotype A12 lacking the leader proteinase-coding region (A12-LLV2) was attenuated and induced an immune response that partially protected cattle from FMD. Animals vaccinated with chemically inactivated A12-LLV2 or wild-type (WT) virus in oil adjuvant developed high levels of neutralizing antibodies and were protected from FMD upon challenge. Intramuscular vaccination of BEI-inactivated virus in adjuvant (both induced high neutralizing antibody titers (Table I) and these animals had antibodies to the viral structural proteins as detected by RIP (Figure 1) . As expected all animals Figure 3 Immunoprecipitation of viral proteins with serum from swine vaccinated with live or BEI-inactivated A12-LLV2 in the absence of adjuvant.

title:
  Protection of swine by live and inactivated vaccines prepared from a leader proteinase-deficient serotype A12 foot-and-mouth disease virus

abstract:
  Abstract Previously, we demonstrated that a genetically engineered variant of foot-and-mouth disease virus (FMDV) serotype A12 lacking the leader proteinase-coding region (A12-LLV2) was attenuated and induced an immune response that partially protected cattle from FMD. In this study, A12-LLV2 was tested in swine as a live or chemically inactivated vaccine. Animals vaccinated with chemically inactivated A12-LLV2 or wild-type (WT) virus in oil adjuvant developed high levels of neutralizing antibodies and were protected from FMD upon challenge. Animals vaccinated with live A12-LLV2 did not exhibit signs of FMD, did not spread virus to other animals, developed a neutralizing antibody response and antibodies to nonstructural protein 3D, and were partially protected from FMD. Animals given a similar dose of chemically inactivated A12-LLV2 in the absence of adjuvant developed a poor immune response and were not protected from FMD, indicating that limited replication was responsible for the improved immune response found in animals vaccinated with live A12-LLV2. The results demonstrate the potential of A12-LLV2 as a live-attenuated vaccine as well as a safe source of antigen for chemically inactivated vaccines.


id: cord-260145-grz0fe9l
author: Liu, Shengwang
date: 2009-07-23
txt: ./txt/cord-260145-grz0fe9l.txt
cache: ./cache/cord-260145-grz0fe9l.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1016/j.vaccine.2009.05.072
doi: 10.1016/j.vaccine.2009.05.072
summary:
  title: Altered pathogenicity, immunogenicity, tissue tropism and 3′-7 kb region sequence of an avian infectious bronchitis coronavirus strain after serial passage in embryos In this study, we attenuated a Chinese LX4-type nephropathogenic infectious bronchitis virus (IBV) strain, CK/CH/LHLJ/04V, by serial passage in embryonated chicken eggs. At the age of 15 days, groups 1-4 were inoculated intranasally with 0.1 ml per chick containing 10 4.7 -10 4.8 median embryo infectious doses (EID 50 ) at passage level 3 of strains CH/CK/LHLJ/04V, CK/CH/LDL/04II, CK/CH/LXJ/02I and CK/CH/LSHH/03I. The CH/CK/LHLJ/04V strain was serially passaged 110 times by inoculating 9-day-old SPF chicken eggs by the allantoic cavity route as described previously [19] . Virus titrations were performed in 9-day-old embryonated chicken SPF eggs via the allantoic cavity route of inoculation, and titers were expressed as 50% (median) embryo infectious doses (EID 50 ) [9, 37] .

title:
  Altered pathogenicity, immunogenicity, tissue tropism and 3′-7 kb region sequence of an avian infectious bronchitis coronavirus strain after serial passage in embryos

abstract:
  In this study, we attenuated a Chinese LX4-type nephropathogenic infectious bronchitis virus (IBV) strain, CK/CH/LHLJ/04V, by serial passage in embryonated chicken eggs. Based on sequence analysis of the 3′-7 kb region, the CK/CH/LHLJ/04V virus population contained subpopulations with a mixture of genetic mutants. The titers of the virus increased gradually during serial passage, but the replication capacity decreased in chickens. The virus was partially attenuated at passage 40 (P40) and P70, and was fully attenuated at P110. It lost immunogenicity and kidney tropism at P110 and P70, respectively. Amino acid substitutions were found in the 3′-7 kb region, primarily in the spike (S) protein. Substitutions in the S1 subunit occurred between P3 and P40 and all subpopulations in a virus passage showed the same substitutions. Other substitutions that occurred between P70 and P110, however, were found only in some subpopulations of the virus passages. A 109-bp deletion in the 3′-UTR was observed in most subpopulations of P70 and P110, and might be related to virus replication, transcription and pathogenicity. The changes described in the 3′-7 kb region of the virus are possibly responsible for virus attenuation, immunogenicity decrease and tissue tropism changes; however, we cannot exclude the possibility that other parts of the genome may also be involved in those changes.


id: cord-260334-xo8ruswo
title: Antibody-mediated protection against MERS-CoV in the murine model()
author: New, R.R.C.
date: 2019-07-09
txt: ./txt/cord-260334-xo8ruswo.txt
cache: ./cache/cord-260334-xo8ruswo.txt
extension: .txt
mime: text/plain
url: https://api.elsevier.com/content/article/pii/S0264410X1930711X
doi: 10.1016/j.vaccine.2019.05.074
summary:
  Murine antisera with neutralising activity for the coronavirus causative of Middle East respiratory syndrome (MERS) were induced by immunisation of Balb/c mice with the receptor binding domain (RBD) of the viral Spike protein. To test the neutralising capacity of these antisera in vivo, susceptibility to MERS-CoV was induced in naive recipient Balb/c mice by the administration of an adenovirus vector expressing the human DPP4 receptor (Ad5-hDPP4) for MERS-CoV, prior to the passive transfer of the RBD-specific murine antisera to the transduced mice. The data gained indicate that this dual-route vaccination with novel formulations of the RBD-Fc, induced systemic and mucosal anti-viral immunity with demonstrated in vitro and in vivo neutralisation capacity for clinical strains of MERS-CoV. We have used this transduced mouse model to test the capacity of the antiserum derived from the dual route immunisation to neutralise MERS-CoV in vivo, by passive transfer prior to challenge with the EMC2012 strain and we have demonstrated a significant reduction in viral load in lung tissue in transduced mice.

abstract:
  Murine antisera with neutralising activity for the coronavirus causative of Middle East respiratory syndrome (MERS) were induced by immunisation of Balb/c mice with the receptor binding domain (RBD) of the viral Spike protein. The murine antisera induced were fully-neutralising in vitro for two separate clinical strains of the MERS coronavirus (MERS-CoV). To test the neutralising capacity of these antisera in vivo, susceptibility to MERS-CoV was induced in naive recipient Balb/c mice by the administration of an adenovirus vector expressing the human DPP4 receptor (Ad5-hDPP4) for MERS-CoV, prior to the passive transfer of the RBD-specific murine antisera to the transduced mice. Subsequent challenge of the recipient transduced mice by the intra-nasal route with a clinical isolate of the MERS-CoV resulted in a significantly reduced viral load in their lungs, compared with transduced mice receiving a negative control antibody. The murine antisera used were derived from mice which had been primed sub-cutaneously with a recombinant fusion of RBD with a human IgG Fc tag (RBD-Fc), adsorbed to calcium phosphate microcrystals and then boosted by the oral route with the same fusion protein in reverse micelles. The data gained indicate that this dual-route vaccination with novel formulations of the RBD-Fc, induced systemic and mucosal anti-viral immunity with demonstrated in vitro and in vivo neutralisation capacity for clinical strains of MERS-CoV.


id: cord-260667-5aurua6o
author: Falchieri, Marco
date: 2013-05-24
url: https://doi.org/10.1016/j.vaccine.2013.03.055
doi: 10.1016/j.vaccine.2013.03.055
title:
  Avian metapneumoviruses expressing Infectious Bronchitis virus genes are stable and induce protection

abstract:
  The study investigates the ability of subtype A Avian metapneumovirus (AMPV) to accept foreign genes and be used as a vector for delivery of Infectious bronchitis virus (IBV) QX genes to chickens. Initially the GFP gene was added to AMPV at all gene junctions in conjunction with the development of cassetted full length DNA AMPV copies. After recombinant virus had been recovered by reverse genetics, GFP positions supporting gene expression while maintaining virus viability in vitro, were determined. Subsequently, either S1 or nucleocapsid (N) genes of IBV were positioned between AMPV M and F genes, while later a bivalent recombinant was prepared by inserting S1 and N at AMPV MF and GL junctions respectively. Immunofluorescent antibody staining showed that all recombinants expressed the inserted IBV genes in vitro and furthermore, all recombinant viruses were found to be highly stable during serial passage. Eyedrop inoculation of chickens with some AMPV-IBV recombinants at one-day-old induced protection against virulent IBV QX challenge 3 weeks later, as assessed by greater motility of tracheal cilia from chickens receiving the recombinants. Nonetheless evidence of AMPV/IBV seroconversion, or major recombinant tracheal replication, were largely absent.


id: cord-260761-ngms51ie
author: Sawada, Akihito
date: 2011-02-04
txt: ./txt/cord-260761-ngms51ie.txt
cache: ./cache/cord-260761-ngms51ie.txt
extension: .txt
mime: text/plain
url: https://api.elsevier.com/content/article/pii/S0264410X10017809
doi: 10.1016/j.vaccine.2010.12.028
summary:
  title: AIK-C measles vaccine expressing fusion protein of respiratory syncytial virus induces protective antibodies in cotton rats When cotton rats immunized with MVAIK/RSV/G were challenged with RSV subgroup A, low levels of infectious virus were recovered from lung. Reverse genetics of the AIK-C live attenuated vaccine was performed and in this study, recombinant AIK-C MV vaccine strains encoding the RSV G or F protein were constructed, and immunogenicity and protective effects against RSV were investigated in cotton rats immunized with recombinant measles vaccines, expressing RSV G or F protein. Cotton rats were sacrificed 10 days after immunization with MVAIK/RSV/G and F, and samples of liver, kidney, spleen, lung, thymus, and nasal turbinate were obtained to detect the MV genome. The recombinant measles virus (MVAIK) triggered an immune response three weeks after vaccination in cotton rats. In non-immunized cotton rats, 10 5.4 and 10 4.5 PFU of infectious virus were recovered from 20 mg of lung tissue four days after the RSV challenge.

title:
  AIK-C measles vaccine expressing fusion protein of respiratory syncytial virus induces protective antibodies in cotton rats

abstract:
  Abstract Respiratory syncytial virus (RSV) is the most common cause of respiratory infection in infants, and no vaccine is available. In this report, recombinant AIK-C measles vaccines, expressing the RSV G or F protein of subgroup A (MVAIK/RSV/G or F), were investigated as a RSV vaccine candidate. MVAIK/RSV/G or F had the original ts phenotype and expressed RSV/G or F protein. Cross-reactive neutralizing antibodies against RSV subgroups A and B were detected in cotton rats immunized intramuscularly with MVAIK/RSV/F but not MVAIK/RSV/G. In cotton rats infected with RSV, RSV was recovered and lung histopathological finding was compatible with interstitial pneumonia, demonstrating thickening of alveolar walls and infiltration of mononuclear cells. When cotton rats immunized with MVAIK/RSV/F were challenged with homologous RSV subgroup A, no infectious RSV was recovered and very mild inflammation was noted without RSV antigen expression. When they were challenged with subgroup B, protective efficacy decreased. When cotton rats immunized with MVAIK/RSV/G were challenged with RSV subgroup A, low levels of infectious virus were recovered from lung. When challenged with subgroup B, no protective effects was demonstrated, demonstrating large amounts of RSV antigen in bronchial-epithelial cells. MVAIK/RSV/F is promising candidate and protective effects should be confirmed in monkey model.


id: cord-261274-y74smbtd
title: Lactogenic immunity following vaccination of cattle with bovine coronavirus
author: Crouch, C. F
date: 2000-09-15
url: https://www.ncbi.nlm.nih.gov/pubmed/10930672/
doi: 10.1016/s0264-410x(00)00177-8
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-262542-vevsgkp6
author: Alharbi, Naif Khalaf
date: 2017-06-27
txt: ./txt/cord-262542-vevsgkp6.txt
cache: ./cache/cord-262542-vevsgkp6.txt
extension: .txt
mime: text/plain
url: https://www.sciencedirect.com/science/article/pii/S0264410X17306564
doi: 10.1016/j.vaccine.2017.05.032
summary:
  title: ChAdOx1 and MVA based vaccine candidates against MERS-CoV elicit neutralising antibodies and cellular immune responses in mice A single dose of ChAdOx1 MERS with tPA elicited cellular immune responses as well as neutralising antibodies that were boosted to a significantly higher level by MVA MERS. Here, we report development of MERS-CoV vaccine candidates that are based on two different viral vectors: Chimpanzee Adenovirus, Oxford University #1 (ChAdOx1) [26] and Modified Vaccinia virus Ankara (MVA) [27, 28] . Previously, we reported the ability of the strong early F11 promoter to enhance cellular immunogenicity of vaccine antigen candidates for malaria and influenza, as compared to utilising p7.5 or mH5 early/late promoters which resulted in a lower level of gene expression immediately after virus infection of target cells, but higher levels at a later stage [31] .

title:
  ChAdOx1 and MVA based vaccine candidates against MERS-CoV elicit neutralising antibodies and cellular immune responses in mice

abstract:
  Abstract The Middle East respiratory syndrome coronavirus (MERS-CoV) has infected more than 1900 humans, since 2012. The syndrome ranges from asymptomatic and mild cases to severe pneumonia and death. The virus is believed to be circulating in dromedary camels without notable symptoms since the 1980s. Therefore, dromedary camels are considered the only animal source of infection. Neither antiviral drugs nor vaccines are approved for veterinary or medical use despite active research on this area. Here, we developed four vaccine candidates against MERS-CoV based on ChAdOx1 and MVA viral vectors, two candidates per vector. All vaccines contained the full-length spike gene of MERS-CoV; ChAdOx1 MERS vaccines were produced with or without the leader sequence of the human tissue plasminogen activator gene (tPA) where MVA MERS vaccines were produced with tPA, but either the mH5 or F11 promoter driving expression of the spike gene. All vaccine candidates were evaluated in a mouse model in prime only or prime-boost regimens. ChAdOx1 MERS with tPA induced higher neutralising antibodies than ChAdOx1 MERS without tPA. A single dose of ChAdOx1 MERS with tPA elicited cellular immune responses as well as neutralising antibodies that were boosted to a significantly higher level by MVA MERS. The humoral immunogenicity of a single dose of ChAdOx1 MERS with tPA was equivalent to two doses of MVA MERS (also with tPA). MVA MERS with mH5 or F11 promoter induced similar antibody levels; however, F11 promoter enhanced the cellular immunogenicity of MVA MERS to significantly higher magnitudes. In conclusion, our study showed that MERS-CoV vaccine candidates could be optimized by utilising different viral vectors, various genetic designs of the vectors, or different regimens to increase immunogenicity. ChAdOx1 and MVA vectored vaccines have been safely evaluated in camels and humans and these MERS vaccine candidates should now be tested in camels and in clinical trials.


id: cord-262940-eyejnexx
author: Liu, Genmei
date: 2013-11-12
txt: ./txt/cord-262940-eyejnexx.txt
cache: ./cache/cord-262940-eyejnexx.txt
extension: .txt
mime: text/plain
url: https://www.sciencedirect.com/science/article/pii/S0264410X13012656
doi: 10.1016/j.vaccine.2013.09.024
summary:
  In the present study, we assembled IBV VLPs containing M and S proteins using a baculovirus expression system and we further evaluated the VLPs immune responses in mice and chickens. The results showed that, 2 weeks after the primary vaccination (day 14), both of VLPs and inactivated H120 groups could not detected serum IgG titers, and the differences between these and PBS groups were not statistically significant (P > 0.05); but following the second immunization (day 28), the IgG titers of the VLPs and inactivated H120 groups increased (Fig. 6 ) and were significantly higher (P < 0.01) than the PBS group. The results showed that VLPs and inactivated H120 groups had statistically significantly higher neutralizing antibody titers (P < 0.01) than the PBS group (Fig. 7) . Virus like particles (VLPs) and inactivated H120 groups had significantly higher neutralizing antibody titers (P < 0.01) than the PBS group.

title:
  Assembly and immunogenicity of coronavirus-like particles carrying infectious bronchitis virus M and S proteins

abstract:
  Infectious bronchitis virus (IBV) as an avian coronavirus is still posing a persistent and imminent threat to the poultry industry worldwide. Here we report that transfection of Sf9 cells with a single recombinant baculovirus encoding M and S proteins resulted in the assembly of IBV VLPs; this is the first report that S protein plus M protein alone were able to be assembled into VLPs for coronaviruses. We further showed that the generated IBV VLPs could induce humoral immune responses in a level comparable to that of inactivated IBV vaccine, and more importantly the IBV VLPs could elicit significantly higher cellular immune responses than the inactivated IBV vaccine. In summary, the assembly of IBV VLPs with M and S proteins provided a simple strategy for generating VLPs for coronaviruses, and the generated IBV VLPs laid a feasible foundation for the development of an effective vaccine against infection of IBV in the future.


id: cord-263443-m98qisld
title: Caregiver willingness to vaccinate their children against COVID-19: cross sectional survey
author: Goldman, Ran D.
date: 2020-10-10
txt: ./txt/cord-263443-m98qisld.txt
cache: ./cache/cord-263443-m98qisld.txt
extension: .txt
mime: text/plain
url: https://api.elsevier.com/content/article/pii/S0264410X20313177
doi: 10.1016/j.vaccine.2020.09.084
summary:
  title: Caregiver willingness to vaccinate their children against COVID-19: cross sectional survey Purpose To investigate predictors associated with global caregivers'' intent to vaccinate their children against COVID-19, when the vaccine becomes available. A univariate and subsequent multivariate analysis found that increased intended uptake was associated with children that were older, children with no chronic illness, when fathers completed the survey, children up-to-date on their vaccination schedule, recent history of vaccination against influenza, and caregivers concerned their child had COVID-19 at the time of survey completion in the ED. Conclusions The majority of caregivers intend to vaccinate their children against COVID-19, though uptake will likely be associated with specific factors such as child and caregiver demographics and vaccination history. Factors associated with uptake of vaccination against 413 pandemic influenza: A systematic review Factors associated with parental 417 acceptance and refusal of pandemic influenza A/H1N1 vaccine in Turkey

abstract:
  Background More than 100 COVID-19 vaccine candidates are in development since the SARS-CoV-2 genetic sequence was published in January 2020. The uptake of a COVID-19 vaccine among children will be instrumental in limiting the spread of the disease as herd immunity may require vaccine coverage of up to 80% of the population. Prior history of pandemic vaccine coverage was as low as 40% among children in the United States during the 2009 H1N1 influenza pandemic. Purpose To investigate predictors associated with global caregivers’ intent to vaccinate their children against COVID-19, when the vaccine becomes available. Method An international cross sectional survey of 1541 caregivers arriving with their children to 16 pediatric Emergency Departments (ED) across six countries from March 26 to May 31, 2020. Results 65% (n = 1005) of caregivers reported that they intend to vaccinate their child against COVID-19, once a vaccine is available. A univariate and subsequent multivariate analysis found that increased intended uptake was associated with children that were older, children with no chronic illness, when fathers completed the survey, children up-to-date on their vaccination schedule, recent history of vaccination against influenza, and caregivers concerned their child had COVID-19 at the time of survey completion in the ED. The most common reason reported by caregivers intending to vaccinate was to protect their child (62%), and the most common reason reported by caregivers refusing vaccination was the vaccine’s novelty (52%). Conclusions The majority of caregivers intend to vaccinate their children against COVID-19, though uptake will likely be associated with specific factors such as child and caregiver demographics and vaccination history. Public health strategies need to address barriers to uptake by providing evidence about an upcoming COVID-19 vaccine’s safety and efficacy, highlighting the risks and consequences of infection in children, and educating caregivers on the role of vaccination.


id: cord-263862-zzys31e9
author: Ryan, Elizabeth J.
date: 2007-04-30
txt: ./txt/cord-263862-zzys31e9.txt
cache: ./cache/cord-263862-zzys31e9.txt
extension: .txt
mime: text/plain
url: https://www.sciencedirect.com/science/article/pii/S0264410X06013880
doi: 10.1016/j.vaccine.2006.12.048
summary:
  Therefore, this leads us to suggest that ALVAC can act as a Th1 polarizing adjuvant by inducing local inflammation [7] , resulting in DC maturation and chemokine production which in turn causes the recruitment of IFN-␥ secreting NK cells. Understanding the mechanism of adjuvant action of ALVAC, will allow more effective targeting of the desired immune response by taking advantage of the fact that ALVAC can be manipulated to encode a variety of immunomodulatory transgenes, e.g. GM-CSF [11] or IL-12 [12] that can further enhance the activation of NK cells or DCs. Six to eight week old female Balb/c ByJ mice (Charles River, Les Oncins, France) or 129/Sv, IFN-␣ receptor knockout and IFN-␥ receptor knockout (B + K Universal, Hull, UK) were used. In order to detect circulating IFN-␣ groups of Balb/c mice were immunised i.m. with 1/10th of the human dose of ALVAC and then bled at various time-points, and the levels of IFN-␣ in the serum were determined by ELISA.

title:
  The Canarypox-virus vaccine vector ALVAC triggers the release of IFN-γ by Natural Killer (NK) cells enhancing Th1 polarization

abstract:
  We investigated the mechanism by which ALVAC activates innate immunity. Combining ALVAC with protein antigens significantly augmented antigen-specific IgG2a responses; this was dependent on the presence of bioactive interferon (IFN)-γ. Immuno-depletion of NK cells prior to ALVAC immunisation abrogated IFN-γ production indicating that they are the main cellular source of early IFN-γ in vivo. Murine bone-marrow derived dendritic cells (BMDCs) cultured in the presence of ALVAC secreted high levels of the chemokines CXCL10 and CCL2 and up-regulated expression of the maturation markers CD40, CD80 and CD86. Therefore, we conclude that ALVAC acts as an adjuvant through a mechanism requiring NK cell derived IFN-γ, DC activation and chemokine secretion.


id: cord-265757-8ces57rn
author: Tondella, M. L.
date: 2009-02-05
txt: ./txt/cord-265757-8ces57rn.txt
cache: ./cache/cord-265757-8ces57rn.txt
extension: .txt
mime: text/plain
url: https://api.elsevier.com/content/article/pii/S0264410X08015946
doi: 10.1016/j.vaccine.2008.11.072
summary:
  The major items included: (1) to identify a group that will organize, prepare, maintain, and distribute proficiency panels and key reagents such as reference and control sera; (2) to encourage the development and identification of one or more reference laboratories that can serve as an anchor and resource for other laboratories; (3) to define a performance-based assay method that can serve as a reference point for evaluating laboratory differences; (4) to develop guidance on quality of other reagents, e.g., pertussis toxin and other antigens, and methods to demonstrate their suitability; (5) to establish an international working group to harmonize the criteria to evaluate the results obtained on reference and proficiency panel sera; (6) to create an inventory to determine the amount of appropriate and well-characterized sera that are available globally to be used as bridging reagents for vaccine licensure; and (7) to seek specific guidance from regulatory authorities regarding the expectations and requirements for the licensure of new multicomponent pertussis vaccines.

title:
  International Bordetella pertussis assay standardization and harmonization meeting report. Centers for Disease Control and Prevention, Atlanta, Georgia, United States, 19–20 July 2007

abstract:
  Abstract An international meeting on Bordetella pertussis assay standardization and harmonization was held at the Centers for Disease Control and Prevention (CDC), Atlanta, GA, 19–20 July 2007. The goal of the meeting was to harmonize the immunoassays used for pertussis diagnostics and vaccine evaluation, as agreed upon by academic and government researchers, regulatory authorities, vaccine manufacturers, and the World Health Organization (WHO). The primary objectives were (1) to provide epidemiologic, laboratory, and statistical background for support of global harmonization; (2) to overview the current status of global epidemiology, pathogenesis and immunology of pertussis; (3) to develop a consensus opinion on existing gaps in understanding standardization of pertussis assays used for serodiagnosis and vaccine evaluation; and (4) to search for a multicenter process for addressing these priority gaps. Presentations and discussions by content experts addressed these objectives. A prioritized list of action items to improve standardization and harmonization of pertussis assays was identified during a group discussion at the end of the meeting. The major items included: (1) to identify a group that will organize, prepare, maintain, and distribute proficiency panels and key reagents such as reference and control sera; (2) to encourage the development and identification of one or more reference laboratories that can serve as an anchor and resource for other laboratories; (3) to define a performance-based assay method that can serve as a reference point for evaluating laboratory differences; (4) to develop guidance on quality of other reagents, e.g., pertussis toxin and other antigens, and methods to demonstrate their suitability; (5) to establish an international working group to harmonize the criteria to evaluate the results obtained on reference and proficiency panel sera; (6) to create an inventory to determine the amount of appropriate and well-characterized sera that are available globally to be used as bridging reagents for vaccine licensure; and (7) to seek specific guidance from regulatory authorities regarding the expectations and requirements for the licensure of new multicomponent pertussis vaccines.


id: cord-266204-ipa017wz
title: Personalized vaccinology: A review
author: Poland, G. A.
date: 2018-08-28
txt: ./txt/cord-266204-ipa017wz.txt
cache: ./cache/cord-266204-ipa017wz.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/28774561/
doi: 10.1016/j.vaccine.2017.07.062
summary:
  This has advanced the science beyond that of reductionist scientific approaches by revealing novel interactions between and within the immune system and other biological systems (beyond transcriptional level), which are critical to developing "downstream" adaptive humoral and cellular responses to infectious pathogens and vaccines. A decade ago, we described the idea of vaccinomics and adversomics, based on the immune response network theory [5, 6] , which utilizes immunogenetics/imunogenomics and systems biology approaches to understand the basis for inter-individual variations in vaccineinduced immune responses in humans, as well as the basis for adverse side effects from vaccines [7] . Published data reveal that innate and adaptive immunity is decreased with age, but the systems-level mechanisms for these findings are unclear [66, 68] , particularly in regard to influenza and other viral vaccine responses where the morbidity, mortality, and associated healthcare costs are greater in older individuals [11] .

abstract:
  Abstract At the current time, the field of vaccinology remains empirical in many respects. Vaccine development, vaccine immunogenicity, and vaccine efficacy have, for the most part, historically been driven by an empiric “isolate-inactivate-inject” paradigm. In turn, a population-level public health paradigm of “the same dose for everyone for every disease” model has been the normative thinking in regard to prevention of vaccine-preventable infectious diseases. In addition, up until recently, no vaccines had been designed specifically to overcome the immunosenescence of aging, consistent with a post-WWII mentality of developing vaccines and vaccine programs for children. It is now recognized that the current lack of knowledge concerning how immune responses to vaccines are generated is a critical barrier to understanding poor vaccine responses in the elderly and in immunoimmaturity, discovery of new correlates of vaccine immunogenicity (vaccine response biomarkers), and a directed approach to new vaccine development. The new fields of vaccinomics and adversomics provide models that permit global profiling of the innate, humoral, and cellular immune responses integrated at a systems biology level. This has advanced the science beyond that of reductionist scientific approaches by revealing novel interactions between and within the immune system and other biological systems (beyond transcriptional level), which are critical to developing “downstream” adaptive humoral and cellular responses to infectious pathogens and vaccines. Others have applied systems level approaches to the study of antibody responses (a.k.a. “systems serology”), [1] high-dimensional cell subset immunophenotyping through CyTOF, [2,3] and vaccine induced metabolic changes [4]. In turn, this knowledge is being utilized to better understand the following: identifying who is at risk for which infections; the level of risk that exists regarding poor immunogenicity and/or serious adverse events; and the type or dose of vaccine needed to fully protect an individual. In toto, such approaches allow for a personalized approach to the practice of vaccinology, analogous to the substantial inroads that individualized medicine is playing in other fields of human health and medicine. Herein we briefly review the field of vaccinomics, adversomics, and personalized vaccinology.


id: cord-266745-jit1xeqc
title: Passive protection effect of chicken egg yolk immunoglobulins on enterovirus 71 infected mice
author: Liou, Jenn-Fa
date: 2010-11-29
txt: ./txt/cord-266745-jit1xeqc.txt
cache: ./cache/cord-266745-jit1xeqc.txt
extension: .txt
mime: text/plain
url: https://api.elsevier.com/content/article/pii/S0264410X10014313
doi: 10.1016/j.vaccine.2010.09.089
summary:
  title: Passive protection effect of chicken egg yolk immunoglobulins on enterovirus 71 infected mice The results of the neutralization effect of specific IgY in EV71-challenged mice demonstrate that the EV71-specific IgY, either by intraperitoneal injection or oral administration, was able to significantly reduce the morbidity and mortality in EV71 infected mice pups. This study was subjected to produce IgY against enterovirus 71 (anti-EV71 IgY) and evaluated the inhibition effects of specific IgY on EV71, including in vitro virus neutralization test and in vivo ICR mice model. In trial 1, we challenged 1-day-old mice with a mouse-adapted EV71 strain MP4 by intraperitoneally administering a dosage of 10 5 pfu per mouse, and treated with specific IgY of neutralization titer 64. This indicates that the orally fed specific IgY effectively neutralized the viral attack in the gastroenteric duct, thereby blocking the infection of virus in challenged mice.

abstract:
  The objective of this study is to evaluate the passive protective efficiency of immunoglobulin in yolk (IgY) specific against human enterovirus type 71 (EV71). The antibody was raised by intramuscular immunization to 10 White Leghorn hens, with inactivated human EV71 serving as the antigen. The titer and specificity of the antibody were analyzed from purified IgY in the egg yolks of immunized hens. Results indicate that the titer of IgY specific against EV71 increased from the third week after the first immunization. The content of total IgY was 190 ± 26 mg/yolk, with an average concentration of specific IgY of 6.34 ± 3.38 mg/yolk in the eggs from 3 to 18 wk after immunization. The results of the neutralization effect of specific IgY in EV71-challenged mice demonstrate that the EV71-specific IgY, either by intraperitoneal injection or oral administration, was able to significantly reduce the morbidity and mortality in EV71 infected mice pups.


id: cord-267712-mhx8e5y0
title: Evaluation of attenuated VSVs with mutated M or/and G proteins as vaccine vectors
author: Fang, Xinkui
date: 2012-02-08
txt: ./txt/cord-267712-mhx8e5y0.txt
cache: ./cache/cord-267712-mhx8e5y0.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/22222871/
doi: 10.1016/j.vaccine.2011.12.085
summary:
  Due to its potent capabilities in triggering cellular, humoral, and mucosal immunities in animals, even after a single administration, recombinant VSV has been studied as a vaccine vector not only for preventing vesicular stomatitis disease in livestock [4] , but a number of human pathogens including: Influenza virus, Ebola virus, Marburg virus, Human immunodeficiency (HIV) virus, Severe Acute Respiratory Syndrome (SARS) virus, and Hepatitis C virus [5] [6] [7] [8] [9] . In vivo, however, VSV M protein mutant proved to be only moderately attenuated in experimental infections [16, 21] , whereas there is currently no information available if recombinant VSV with truncated G protein is safe or not when animals challenged with high dose of the mutant virus. Based on pathogenicity and capabilities to stimulate potent immune responses, we aimed to identify a suitable recombinant VSV vaccine vector and vaccine candidate for preventing vesicular stomatitis disease.

abstract:
  Vesicular stomatitis virus (VSV) is a promising vector for vaccine and oncolysis, but it can also produce acute diseases in cattle, horses, and swine characterized by vesiculation and ulceration of the tongue, oral tissues, feet, and teats. In experimental animals (primates, rats, and mice), VSV has been shown to lead to neurotoxicities, such as hind limb paralysis. The virus matrix protein (M) and glycoprotein (G) are both major pathogenic determinants of wild-type VSV and have been the major targets for the production of attenuated strains. Existing strategies for attenuation included: (1) deletion or M51R substitution in the M protein (VSVΔM51 or VSVM51R, respectively); (2) truncation of the C-terminus of the G protein (GΔ28). Despite these mutations, recombinant VSV with mutated M protein is only moderately attenuated in animals, whereas there are no detailed reports to determine the pathogenicity of recombinant VSV with truncated G protein at high dose. Thus, a novel recombinant VSV (VSVΔM51-GΔ28) as well as other attenuated VSVs (VSVΔM51, VSV-GΔ28) were produced to determine their efficacy as vaccine vectors with low pathogenicity. In vitro studies indicated that truncated G protein (GΔ28) could play a more important role than deletion of M51 (ΔM51) for attenuation of recombinant VSV. VSVΔM51-GΔ28 was determined to be the most attenuated virus with low pathogenicity in mice, with VSV-GΔ28 also showing relatively reduced pathogenicity. Further, neutralizing antibodies stimulated by VSV-GΔ28 proved to be significantly higher than in mice treated with VSVΔM51-GΔ28. In conclusion, among different attenuated VSVs with mutated M and/or G proteins, recombinant VSV with only truncated G protein (VSV-GΔ28) demonstrated ideal balance between pathogenesis and stimulating a protective immune response. These properties make VSV-GΔ28 a promising vaccine vector and vaccine candidate for preventing vesicular stomatitis disease.


id: cord-268369-yj7m0n0f
author: Wang, Keyang
date: 2006-03-15
txt: ./txt/cord-268369-yj7m0n0f.txt
cache: ./cache/cord-268369-yj7m0n0f.txt
extension: .txt
mime: text/plain
url: https://api.elsevier.com/content/article/pii/S0264410X05011308
doi: 10.1016/j.vaccine.2005.11.005
summary:
  The influenza hemagglutinin protein (HA), the active ingredient in the current vaccine, can be expressed in insect cells using the baculovirus expression vector system and purified rapidly. On the other hand, the recombinant protein-based approach involves production of viral antigens such as HA and NA in cell culture with recombinant DNA technology and utilization of the purified antigens as the active ingredients in the vaccine. The rHA influenza vaccines developed using the baculovirus-insect cell expression system has been tested in several Phase I and Phase II human clinical trials involving over 1200 subjects that demonstrated safety, immunogenicity and efficacy [19] [20] [21] [22] [23] . On the other hand, most of RBCs were bound to the insect cells infected with baculovirus containing the HA gene derived from influenza strain A/New Caledonia/20/99 (H1N1) (Fig. 1b) .

title:
  Expression and purification of an influenza hemagglutinin—one step closer to a recombinant protein-based influenza vaccine

abstract:
  Numerous human infections with avian influenza viruses in Asia in recent years have raised the concern that the next influenza pandemic is imminent. The most effective way to combat influenza is through the vaccination of the public. However, a minimum of 3–6 months is needed to develop an influenza vaccine using the traditional egg-based vaccine approach. The influenza hemagglutinin protein (HA), the active ingredient in the current vaccine, can be expressed in insect cells using the baculovirus expression vector system and purified rapidly. An influenza vaccine based on such a recombinant antigen allows a more timely response to a potential influenza pandemic. Here, we report an innovative monitoring assay for recombinant HA (rHA) expression and a rapid purification process. Various biochemical analyses indicate that the purified rHA is properly folded and biologically active.


id: cord-269448-1jikrn37
title: Immunogenicity assay of the Leishmune(®) vaccine against canine visceral leishmaniasis in Brazil
author: Borja-Cabrera, G.P.
date: 2008-09-15
txt: ./txt/cord-269448-1jikrn37.txt
cache: ./cache/cord-269448-1jikrn37.txt
extension: .txt
mime: text/plain
url: https://www.sciencedirect.com/science/article/pii/S0264410X08009730
doi: 10.1016/j.vaccine.2008.07.029
summary:
  The strong immunogenicity induced by Leishmune(®) vaccine was demonstrated by the 98% of FML-seroconversion, increase in absorbencies, the 82.7% DTH positive reactions and increase in skin test size diameters, the average increase in CD8+ total lymphocytes population in blood (27.1%), expected for QS21 saponin-containing vaccine, the sustained proportions of CD4+ T cells, and the average increased proportions of CD21+ B lymphocytes (42.3%). Six hundred healthy dogs from the canine visceral leishmaniasis endemic towns of Araç atuba, Andradina, Valparaíso, Guararapes, Bauru (São Paulo state) and Belo Horizonte, Nova Lima, Sete Lagoas (Minas Gerais state), Brazil, showing previous negative results in Leishmania-serology by the immunofluorescent assay [33] were selected for vaccination with three doses of Leishmune ® (Fort Dodge Animal Health, Campinas, SP, Brazil), in a 21-day interval, through the subcutaneous (sc) route [32] and a booster in month 12.

abstract:
  Leishmune(®) is the industrialized version of the FML-saponin vaccine which has been shown to develop 92–95% protection in vaccinated dogs and 76–80% vaccine efficacy against field canine visceral leishmaniasis (CVL) in Brazil. Leishmune(®) has been proven to be safe and tolerable and a transmission-blocking vaccine which renders vaccinated dogs non-infectious to sand fly vectors. In the present investigation, 550 healthy seronegative dogs of endemic and epidemic areas of Brazil were monitored for Leishmune(®)-induced immunogenicity during a 2-year trial. Another group of 588 untreated exposed dogs was also studied in parallel. Both groups were seronegative on day 0. The strong immunogenicity induced by Leishmune(®) vaccine was demonstrated by the 98% of FML-seroconversion, increase in absorbencies, the 82.7% DTH positive reactions and increase in skin test size diameters, the average increase in CD8+ total lymphocytes population in blood (27.1%), expected for QS21 saponin-containing vaccine, the sustained proportions of CD4+ T cells, and the average increased proportions of CD21+ B lymphocytes (42.3%). The Leishmune(®)-induced protection against CVL is demonstrated by the results: 98.8% asymptomatic dogs (at the end of first year) and 99% healthy survivors (at the end of the second year) among vaccinated dogs, compared to the 79.4% asymptomatic and 61% survivor dogs (p < 0.001) monitored in the untreated exposed cohort. In spite of the low vaccine coverage, it was possible to detect a 66.1% (p < 0.005) reduction in Belo Horizonte and an 80.2% (p < 0.005) reduction in Araçatuba of the incidence of CVL among vaccinated dogs, when compared to the global incidence of CVL of each town, respectively. Our preliminary results support the potential use of Leishmune(®) to prevent CVL epidemics.


id: cord-270910-xb746mv5
author: Lebrun-Harris, Lydie A.
date: 2020-07-24
url: https://www.sciencedirect.com/science/article/pii/S0264410X20309348
doi: 10.1016/j.vaccine.2020.07.021
title:
  Influenza vaccination among U.S. pediatric patients receiving care from federally funded health centers

abstract:
  INTRODUCTION: During the 2018–2019 influenza season, vaccination coverage among U.S. children was 62.6%. The purpose of this study was to estimate the prevalence of influenza vaccinations among pediatric patients seen in U.S. health centers, and to explore potential disparities in vaccination coverage among subpopulations. Funded by the Health Resources and Services Administration (HRSA) within the U.S. Department of Health and Human Services, these health centers provide primary and preventive care to underserved and vulnerable individuals and families in order to reduce health disparities based on economic, geographic, or cultural barriers. METHODS: Cross-sectional data, analyzed in 2019, came from the most recent waves of the Health Center Patient Survey (2009, 2014). The sample consisted of children ages 2–17 years receiving care from HRSA-funded health centers. The outcome of interest was self- or parent-reported receipt of influenza vaccine in the past year. Multivariable logistic regression was used to estimate the adjusted prevalence rate ratios for the association between demographic characteristics (age, sex, race/ethnicity, poverty level, urban/rural residence, geographic region), health-related variables (receipt of well-child check-up, asthma diagnosis), and influenza vaccination. RESULTS: Influenza vaccination coverage among pediatric health center patients increased from 46.6% in 2009 to 67.8% in 2014. In the adjusted model for 2014, there were few statistically significant differences in vaccination coverage among subpopulation groups, however American Indian/Alaska Native children had 31% increased vaccination coverage compared with non-Hispanic White children (aPRR: 1.31, 95% CI: 1.02–1.60) and children living in the South had 26% decreased vaccination coverage compared with those living in the Northeast (aPRR: 0.74, 95% CI: 0.54–0.93). CONCLUSIONS: Influenza vaccination coverage among pediatric health center patients in 2014 exceeded the national average (as of 2018–2019), and few differences were found among at-risk subpopulations. HRSA-funded health centers are well-positioned to further increase the vaccination rate among children living in underserved communities.


id: cord-271076-436nxsua
title: Emerging diseases, zoonoses and vaccines to control them
author: Paul-Pierre, Pastoret
date: 2009-10-30
txt: ./txt/cord-271076-436nxsua.txt
cache: ./cache/cord-271076-436nxsua.txt
extension: .txt
mime: text/plain
url: https://api.elsevier.com/content/article/pii/S0264410X0900872X
doi: 10.1016/j.vaccine.2009.06.021
summary:
  In Northern America, the spectacular spread of West Nile virus infection, another vector transmitted disease, in humans and horses, was rapidly followed by the development of several vaccines, including a DNA-based vaccine for horses. To prevent Nipah virus (Henipavirus) infection in pigs a vaccine has recently been developed but, unfortunately, in countries like Bangladesh, humans are directly infected by the reservoir, a fruit bat species. The changes following globalisation, climatic change [6, 7] , and the opening of previously closed ecosystems, have considerably modified the pattern of endemic (or enzootic) infections/diseases, and contributed to the emergence of new agents that are pathogenic for humans and domestic animals. It is even more true when facing a really emerging disease that moreover is zoonotic such as Nipah virus infection [27] for which no vaccine was available yet, because the causative agent was previously unknown; the only solution is once again to kill and destroy the infected and in-contact animals.

abstract:
  Abstract Vaccination, when available, is undoubtedly the most cost-effective means of preventing and controlling, and even eradicating, infectious diseases. In recent years vaccination has also been used for other purposes in animal health, production and welfare, e.g. immunocastration. Vaccination of animals serves many different purposes, such as controlling animal infections and infestations, thus improving animal health and welfare; controlling anthropozoonoses and food poisoning in humans, thereby protecting public health; solving problems associated with antibiotic and anthelmintic resistance; helping to leave food-producing animals free of chemical residues; protecting the environment and biodiversity and ensuring animal farming sustainability. The problem is nevertheless more complex when facing emerging or re-emerging infections particularly zoonotic ones.


id: cord-271153-c0aw6jkz
title: Archetype analysis of older adult immunization decision-making and implementation in 34 countries
author: Privor-Dumm, Lois
date: 2020-05-27
txt: ./txt/cord-271153-c0aw6jkz.txt
cache: ./cache/cord-271153-c0aw6jkz.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/32376108/
doi: 10.1016/j.vaccine.2020.04.027
summary:
  Considering common barriers and facilitators of decision-making and implementation of adult vaccines within a primary archetype could help provide a framework for strategies to support countries with similar needs and approaches. Considering common barriers and facilitators of decision-making and implementation of adult vaccines within a primary archetype could help provide a framework for strategies to support countries with similar needs and approaches. By characterizing groups of countries by features other than disease burden, geography or demographics, the analysis seeks to support global efforts to address country needs in strengthening processes for vaccine decision-making and implementation; facilitating sharing of best practices amongst countries with similar characteristics; and providing evidence, system or advocacy support to help countries succeed within their specific context. Domains (Table 1) were identified as part of a framework of potential barriers and facilitators for adult vaccine decisionmaking: country characteristics, adult vaccine/aging policies and decision-making, health immunization systems, uptake, and stakeholders and champions.

abstract:
  The global population of adults over 65 years of age is growing rapidly and is expected to double by 2050. Countries will face substantial health, economic and social burden deriving from vaccine-preventable diseases (VPDs) such as influenza, pneumonia and herpes zoster in older adults. It will be essential that countries utilize several public health strategies, including immunization. Understanding the different approaches countries have taken on adult immunization could help provide future learnings and technical support for adult vaccines within life-course immunization strategies. In this study, we describe the priorities and approaches that underlie adult immunization decision-making and implementation processes in 32 high-and-middle-income countries and two territories (“34 countries”) who recommend adult vaccines in their national schedule. We conducted an archetype analysis based on a subset of two dozen indicators abstracted from a larger database. The analysis was based on a mixed-methods study, including results from 120 key informant interviews in six countries and a landscape review of secondary data from 34 countries. We found four distinct archetypes: disease prevention-focused; health security-focused; evolving adult focus; and, child-focused and cost-sensitive. The highest performing countries belonged to the disease prevention-focused and health security archetypes, although there was a range of performance within each archetype. Considering common barriers and facilitators of decision-making and implementation of adult vaccines within a primary archetype could help provide a framework for strategies to support countries with similar needs and approaches. It can also help in developing context-specific policies and guidance, including for countries prioritizing adult immunization programs in light of COVID-19. Further research may be beneficial to further refine archetypes and expand the understanding of what influences success within them. This can help advance policies and action that will improve vaccine access for older adults and build a stronger appreciation of the value of immunization amongst a variety of stakeholders.


id: cord-271514-sls3bsm0
title: Ensemble Forecast Modeling for the Design of COVID-19 Vaccine Efficacy Trials
author: Dean, Natalie E.
date: 2020-09-15
url: https://www.ncbi.nlm.nih.gov/pubmed/33012602/
doi: 10.1016/j.vaccine.2020.09.031
abstract:
  To rapidly evaluate the safety and efficacy of COVID-19 vaccine candidates, prioritizing vaccine trial sites in areas with high expected disease incidence can speed endpoint accrual and shorten trial duration. Mathematical and statistical forecast models can inform the process of site selection, integrating available data sources and facilitating comparisons across locations. We recommend the use of ensemble forecast modeling – combining projections from independent modeling groups – to guide investigators identifying suitable sites for COVID-19 vaccine efficacy trials. We describe an appropriate structure for this process, including minimum requirements, suggested output, and a user-friendly tool for displaying results. Importantly, we advise that this process be repeated regularly throughout the trial, to inform decisions about enrolling new participants at existing sites with waning incidence versus adding entirely new sites. These types of data-driven models can support the implementation of flexible efficacy trials tailored to the outbreak setting.


id: cord-271650-biq0chyn
author: Torres, Juan M
date: 2000-09-15
txt: ./txt/cord-271650-biq0chyn.txt
cache: ./cache/cord-271650-biq0chyn.txt
extension: .txt
mime: text/plain
url: https://www.sciencedirect.com/science/article/pii/S0264410X00001833
doi: 10.1016/s0264-410x(00)00183-3
summary:
  title: Safety evaluation of a recombinant myxoma-RHDV virus inducing horizontal transmissible protection against myxomatosis and rabbit haemorrhagic disease Safety evaluation of a recombinant myxoma-RHDV virus inducing horizontal transmissible protection against myxomatosis and rabbit haemorrhagic disease In order to protect wild rabbits against both myxomatosis and RHD, we constructed a recombinant virus based on the naturally attenuated MV ®eld strain 6918 [24] , that expressed the RHDV VP60 protein [25] . Groups of eight wild rabbits (2 month old, weighing around 0.8 kg) free from MV and RHDV antibodies, were inoculated at the back by intradermic (i.d.) or subcutaneous (s.c.) route with dierent doses of the vaccine (10 4 , 10 5 , 10 6 pfu of 6918VP60-T2 recombinant virus). Treated rabbits were inoculated (by s.c or i.d. route) with 10 4 pfu of 6918VP60-T2 virus, and clinical signs due to virus infection were compared with those induced in control rabbits, which were vaccinated but not treated with prednisolone (Fig 2, Table 3 ).

title:
  Safety evaluation of a recombinant myxoma-RHDV virus inducing horizontal transmissible protection against myxomatosis and rabbit haemorrhagic disease

abstract:
  We have recently developed a transmissible vaccine to immunize rabbits against myxomatosis and rabbit haemorrhagic disease based on a recombinant myxoma virus (MV) expressing the rabbit haemorrhagic disease virus (RHDV) capsid protein [Bárcena et al. Horizontal transmissible protection against myxomatosis and rabbit haemorragic disease using a recombinant myxoma virus. J. Virol. 2000;74:1114–23]. Administration of the recombinant virus protects rabbits against lethal RHDV and MV challenges. Furthermore, the recombinant virus is capable of horizontal spreading promoting protection of contact animals, thus providing the opportunity to immunize wild rabbit populations. However, potential risks must be extensively evaluated before considering its field use. In this study several safety issues concerning the proposed vaccine have been evaluated under laboratory conditions. Results indicated that vaccine administration is safe even at a 100-fold overdose. No undesirable effects were detected upon administration to immunosuppressed or pregnant rabbits. The recombinant virus maintained its attenuated phenotype after 10 passages in vivo.


id: cord-271734-1cfhjuxi
author: Vergkizi, Souzan
date: 2020-10-16
url: https://api.elsevier.com/content/article/pii/S0264410X20312846
doi: 10.1016/j.vaccine.2020.10.009
title:
  Bacillus Calmette–Guérin (BCG) vaccine generates immunoregulatory cells in the cervical lymph nodes in guinea pigs injected intra dermally

abstract:
  This work demonstrates the presence of immune regulatory cells in the cervical lymph nodes draining Bacillus Calmette-Guérin (BCG) vaccinated site on the dorsum of the ear in guinea pigs. It is shown that whole cervical lymph node cells did not proliferate in vitro in the presence of soluble mycobacterial antigens (PPD or leprosin) despite being responsive to whole mycobacteria. Besides, T cells from these lymph nodes separated as a non-adherent fraction on a nylon wool column, proliferated to PPD in the presence of autologous antigen presenting cells. Interestingly, addition of as low as 20% nylon wool adherent cells to these, sharply decreased the proliferation by 83%. Looking into what cells in the adherent fraction suppressed the proliferation, it was found that neither the T cell nor the macrophage enriched cell fractions of this population individually showed suppressive effect, indicating that their co-presence was necessary for the suppression. Since BCG induced granulomas resolve much faster than granulomas induced by other mycobacteria such as Mycobacterium leprae the present experimental findings add to the existing evidence that intradermal BCG vaccination influences subsequent immune responses in the host and may further stress upon its beneficial role seen in Covid-19 patients.


id: cord-272292-k0ugjb6f
title: Immunological characterizations of the nucleocapsid protein based SARS vaccine candidates
author: Liu, Shih-Jen
date: 2006-04-12
txt: ./txt/cord-272292-k0ugjb6f.txt
cache: ./cache/cord-272292-k0ugjb6f.txt
extension: .txt
mime: text/plain
url: https://api.elsevier.com/content/article/pii/S0264410X06000879
doi: 10.1016/j.vaccine.2006.01.058
summary:
  The recombinant nucleocapsid (rN) protein of the coronavirus (CoV) responsible for severe acute respiratory syndrome (SARS) was cloned and expressed in Escherichia coli, extracted from cell lysates containing 6 M urea, then purified by Ni(2+)-affinity chromatography. To identify the B-cell immunodominant epitopes of the rN protein in the mouse and monkey, the reactivities of antisera raised against purified rN proteins formulated in ISA-51/CpG were tested with a panel of overlapping synthetic peptides covering the entire N protein sequence. We also only observed that peptides corresponding to residues 336–350 were capable of stimulating IFN-γ production in T-cell cultures derived from peripheral blood mononuclear cells (PBMCs) of macaques immunized with the rN protein emulsified in ISA/CpG adjuvant.

abstract:
  The recombinant nucleocapsid (rN) protein of the coronavirus (CoV) responsible for severe acute respiratory syndrome (SARS) was cloned and expressed in Escherichia coli, extracted from cell lysates containing 6 M urea, then purified by Ni(2+)-affinity chromatography. In animal immunogenicity studies, we found that most anti-rN protein antibodies were IgG2a in BALB/c mice vaccinated with rN emulsified in Montanide ISA-51 containing the synthetic oligodeoxynucleotide, CpG. In contrast, anti-rN protein antibodies of mice immunized with rN protein in PBS were found to mainly be IgG1. These results indicated that ISA-51/CpG-formulated rN protein was dramatically biased toward a Th1 immune response. To identify the B-cell immunodominant epitopes of the rN protein in the mouse and monkey, the reactivities of antisera raised against purified rN proteins formulated in ISA-51/CpG were tested with a panel of overlapping synthetic peptides covering the entire N protein sequence. Three immunodominant linear B-cell epitope regions were mapped to residues 166–180, 356–375, and 396–410 of the rN protein. When the reactivities of these peptides were screened with human sera from five SARS patients, peptides corresponding to residues 156–175 reacted strongly with sera from two of the SARS patients. These results indicated that the region around residues 156–175 of the N protein is immunogenic in the mouse, monkey, and human. We found that peptides corresponding to residues 1–30, 86–100, 306–320, and 351–365 contained murine immunodominant T-cell epitopes. To identify functional CTL epitopes of the N protein, BALB/c mice were immunized with peptides containing the H-2K(d) CTL motif emulsified in adjuvant ISA-51/CpG. Using an IFN-γ secretion cell assay and analysis by flow cytometry, peptides containing residues 81–95 were found to be capable of stimulating both CD4(+) and CD8(+) cell proliferation in vitro. We also only observed that peptides corresponding to residues 336–350 were capable of stimulating IFN-γ production in T-cell cultures derived from peripheral blood mononuclear cells (PBMCs) of macaques immunized with the rN protein emulsified in ISA/CpG adjuvant. Our current results together with those of others suggest that some immunodominant B-cell and T-cell epitopes are conserved in the mouse, monkey, and human. This information is very important for the development SARS diagnostic kits and a vaccine.


id: cord-273065-peqz7okh
title: Arboviruses: A global public health threat
author: Girard, Marc
date: 2020-04-24
txt: ./txt/cord-273065-peqz7okh.txt
cache: ./cache/cord-273065-peqz7okh.txt
extension: .txt
mime: text/plain
url: https://www.sciencedirect.com/science/article/pii/S0264410X20304709
doi: 10.1016/j.vaccine.2020.04.011
summary:
  The repeated occurrence of recent deadly epidemics strongly reinforces the call for action against these viral diseases, and the need for developing effective vaccines, drugs, vector control tools and strong prevention programs. The recent outbreak of neurological disorders and neonatal malformations associated with Zika virus (ZIKV) infection in Latin America {5}, the yellow fever (YFV) epidemics in Angola and Brazil with importation to China [6] , the ever-expanding West Nile virus (WNV) epidemic in the Americas [7] , the recent emergence in East Africa and global spread of chikungunya virus (CHIKV) [8] , as well as the ongoing and expanding dengue virus (DENV) pandemic in the tropics and subtropics [9] have reinforced the call for action in the fight against emerging and re-emerging arboviral diseases. The vaccine showed high efficacy and good safety in seropositive persons in the 9-45 years age group, but a risk of severe dengue was observed in individuals who were naive for DENV infection at the time they were vaccinated.

abstract:
  A conference on «ARBOVIRUSES, A GLOBAL PUBLIC HEALTH THREAT» was organized on June 20–22, 2018 at the Merieux Foundation Conference Center in Veyrier du Lac, France, to review and raise awareness to the global public health threat of epidemic arboviruses, and to advance the discussion on the control and prevention of arboviral diseases. The presentations by scientists and public health officials from Asia, the Americas, Europe and Africa strengthened the notion that arboviral diseases of both humans and domestic animals are progressively becoming dominant public health problems in the world. The repeated occurrence of recent deadly epidemics strongly reinforces the call for action against these viral diseases, and the need for developing effective vaccines, drugs, vector control tools and strong prevention programs.


id: cord-273526-ah0dvnxv
author: Cao, Weiping
date: 2017-06-05
txt: ./txt/cord-273526-ah0dvnxv.txt
cache: ./cache/cord-273526-ah0dvnxv.txt
extension: .txt
mime: text/plain
url: https://api.elsevier.com/content/article/pii/S0264410X1730600X
doi: 10.1016/j.vaccine.2017.05.004
summary:
  Protollin-adjuvanted vaccines elicited enhanced serum protective hemagglutination inhibition titers, mucosal IgA responses, and H5N1-specific cell-mediated immunity that resulted in complete protection against a lethal challenge with a homologous virus as well as a heterologous clade 2 virus A/Indonesia/05/2005 (A/IN/05/05). Our findings suggest that nasal delivery of H5N1 vaccine with Protollin adjuvant can overcome the poor immunogenicity of H5N1 vaccines, induce both cellular and humoral immune responses, enhance protection against challenge with clade 1 and clade 2 H5N1 viruses and achieve significant antigen dose-sparing. Nasal delivery of split, inactivated influenza vaccine generally requires a mucosal adjuvant to induce strong protective immune responses [16] . The breadth of antibody response was also broadened by Protollin-adjuvanted H5N1 vaccine, as they significantly increased serum HI titers against A/IN/05/05 virus compared to the vaccine alone group and fully protected mice against A/IN/05/05 virus challenge.

title:
  Nasal delivery of Protollin-adjuvanted H5N1 vaccine induces enhanced systemic as well as mucosal immunity in mice

abstract:
  Sporadic, yet frequent human infections with avian H5N1 influenza A viruses continue to pose a potential pandemic threat. Poor immunogenicity of unadjuvanted H5N1 vaccines warrants developing novel adjuvants and formulations as well as alternate delivery systems to improve their immunogenicity and efficacy. Here, we show that Protollin, a nasal adjuvant composed of Neisseria meningitides outer membrane proteins non-covalently linked to Shigella flexneri 2a lipopolysaccharide, is a potent nasal adjuvant for an inactivated split virion H5N1 clade 1 A/Viet Nam1203/2004 (A/VN/1203/04) vaccine in a mouse model. Protollin-adjuvanted vaccines elicited enhanced serum protective hemagglutination inhibition titers, mucosal IgA responses, and H5N1-specific cell-mediated immunity that resulted in complete protection against a lethal challenge with a homologous virus as well as a heterologous clade 2 virus A/Indonesia/05/2005 (A/IN/05/05). Detailed analysis of adaptive immunity revealed that Protollin increased the frequency of lymphoid- as well as local tissue-resident antibody-secreting cells, local germinal center reaction of B cells, broad-spectrum of CD4 T cell response. Our findings suggest that nasal delivery of H5N1 vaccine with Protollin adjuvant can overcome the poor immunogenicity of H5N1 vaccines, induce both cellular and humoral immune responses, enhance protection against challenge with clade 1 and clade 2 H5N1 viruses and achieve significant antigen dose-sparing.


id: cord-274110-nyyunoha
title: An inactivated West Nile Virus vaccine derived from a chemically synthesized cDNA system
author: Orlinger, Klaus K.
date: 2010-04-26
txt: ./txt/cord-274110-nyyunoha.txt
cache: ./cache/cord-274110-nyyunoha.txt
extension: .txt
mime: text/plain
url: https://api.elsevier.com/content/article/pii/S0264410X10002860
doi: 10.1016/j.vaccine.2010.02.092
summary:
  A cDNA comprising the complete genome of West Nile Virus (WNV) was generated by chemical synthesis using published sequence data, independent of any preformed viral components. The synthetic WNV, produced by transfection of in vitro transcribed RNA into cell culture, exhibited undistinguishable biological properties compared to the corresponding animal-derived wild-type virus. Taking advantage of the rapid progression of gene synthesis technology (for review [24] ), we intended to adopt such a synthetic approach to produce a flavivirus cDNA system for the generation of a synthetic WNV seed virus for use in vaccine development. The production and characterization of the resulting West Nile Virus, which fully matched the sequence of the in silico designed viral genome, confirms the feasibility and accuracy of the synthetic flavivirus reverse genetic system. Cover slips with fixed cells were dried, rehydrated with phosphate-buffered saline and treated with a polyclonal mouse anti-WNV serum (1:50 dilution) obtained after immunization of mice with a formalin-inactivated whole virus vaccine preparation.

abstract:
  A cDNA comprising the complete genome of West Nile Virus (WNV) was generated by chemical synthesis using published sequence data, independent of any preformed viral components. The synthetic WNV, produced by transfection of in vitro transcribed RNA into cell culture, exhibited undistinguishable biological properties compared to the corresponding animal-derived wild-type virus. No differences were found concerning viral growth in mammalian and insect cell lines and concerning expression of viral proteins in cells. There were also no significant differences in virulence in mice following intranasal challenge. After immunizations of mice with experimental vaccines derived from the synthetic and wild-type viruses, protection from lethal challenge was achieved with similar amounts of antigen. Both vaccine preparations also induced comparable levels of neutralizing antibodies in mice. In addition, the synthetic approach turned out to be very accurate, since the rescued WNV genome contained no undesired mutations. Thus, the first flavivirus based on chemical gene synthesis was indistinguishable from the parent virus. This demonstrates that virus isolates from animal sources are dispensable to derive seed viruses for vaccine production or research.


id: cord-274765-3wzht843
title: Derivation of attenuated porcine epidemic diarrhea virus (PEDV) as vaccine candidate
author: Kweon, Chang-Hee
date: 1999-06-04
txt: ./txt/cord-274765-3wzht843.txt
cache: ./cache/cord-274765-3wzht843.txt
extension: .txt
mime: text/plain
url: https://www.sciencedirect.com/science/article/pii/S0264410X99000596
doi: 10.1016/s0264-410x(99)00059-6
summary:
  The field isolate of porcine epidemic diarrhea virus (PEDV) was serially passaged in Vero cells. The cell passaged PEDV, designated KPEDV-9, was tested for its pathogenicity in the neonatal pigs, immunogenicity and safety in the pregnant sows. The results of this study supported that the attenuated virus derived from serial passage could be applied as vaccine for protecting suckling piglets against PEDV infection. In this study, we investigated the attenuation of PEDV through serial passages in Vero cell cultures and its prophylactic eect in pregnant sows. Nevertheless, when compared with the wild PEDV, the animals inoculated with the high passage level of virus did not show any severe signs of diarrhea or death in piglets, supporting attenuation. Development of an Elispot for the detection of antibody secreting cells against the porcine epidemic diarrhea virus (PEDV) in dierent tissues

abstract:
  The field isolate of porcine epidemic diarrhea virus (PEDV) was serially passaged in Vero cells. The cell passaged PEDV, designated KPEDV-9, was tested for its pathogenicity in the neonatal pigs, immunogenicity and safety in the pregnant sows. The result indicated that KPEDV-9 at the 93rd passage revealed reduced pathogenicity in the neonatal pigs. Pregnant sows inoculated with the attenuated virus showed increased immune responses by ELISA. In addition, delivered piglets were protected from challenge of wild type PEDV. The safety test in pregnant sows indicated that all inoculated animals farrowed the average numbers of litters of piglets. The results of this study supported that the attenuated virus derived from serial passage could be applied as vaccine for protecting suckling piglets against PEDV infection.


id: cord-275337-c3qr15es
author: Wright, Edward
date: 2009-11-27
txt: ./txt/cord-275337-c3qr15es.txt
cache: ./cache/cord-275337-c3qr15es.txt
extension: .txt
mime: text/plain
url: https://api.elsevier.com/content/article/pii/S0264410X09013486
doi: 10.1016/j.vaccine.2009.09.024
summary:
  Here we report the results of the largest virus neutralisation study published to date using the surrogate lentiviral pseudotypes rather than the live native or recombinant rabies virus with field serum samples from Tanzanian dogs. We further increase the utility of our pseudotype neutralisation assay for laboratories undertaking vaccine trials and serosurveillance in resource-limited, rabies endemic countries by exploring the use of lacZ as a reporter gene and incorporating the glycoproteins of a further three lyssavirus "Primary" refers to dogs that had never received a rabies vaccination prior to this study, "booster" refers to dogs that had previously received ≥1 rabies vaccination and "no record" means there was no vaccination history available or taken.

title:
  A robust lentiviral pseudotype neutralisation assay for in-field serosurveillance of rabies and lyssaviruses in Africa

abstract:
  The inflexibility of existing serological techniques for detection of rabies in surveillance constrains the benefit to be gained from many current control strategies. We analysed 304 serum samples from Tanzanian dogs for the detection of rabies antibodies in a pseudotype assay using lentiviral vectors bearing the CVS-11 envelope glycoprotein. Compared with the widely used gold standard fluorescent antibody virus neutralisation assay, a specificity of 100% and sensitivity of 94.4% with a strong correlation of antibody titres (r = 0.915) were observed with the pseudotype assay. To increase the assay's surveillance specificity in Africa we incorporated the envelope glycoprotein of local viruses, Lagos bat virus, Duvenhage virus or Mokola virus and also cloned the lacZ gene to provide a reporter element. Neutralisation assays using pseudotypes bearing these glycoproteins reveal that they provide a greater sensitivity compared to similar live virus assays and will therefore allow a more accurate determination of the distribution of these highly pathogenic infections and the threat they pose to human health. Importantly, the CVS-11 pseudotypes were highly stable during freeze–thaw cycles and storage at room temperature. These results suggest the proposed pseudotype assay is a suitable option for undertaking lyssavirus serosurveillance in areas most affected by these infections.


id: cord-275635-d50bxe7c
author: Yuan, Xiaomin
date: 2015-07-31
txt: ./txt/cord-275635-d50bxe7c.txt
cache: ./cache/cord-275635-d50bxe7c.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1016/j.vaccine.2015.06.057
doi: 10.1016/j.vaccine.2015.06.057
summary:
  To explore the possibility of developing a vaccine against transmissible gastroenteritis virus (TGEV) infection, a recombinant swinepox virus (rSPV-SA) expressing a TGEV protective antigen has been constructed. Results from the passive immunity protection test of new born piglets demonstrated that the recombinant live-vector vaccine, rSPV-SA, could 100% protect piglets from the SPV infection, and there was no significant clinical symptom in the rSPV-SA treatment group during this experiment. Eight one-month-old swine (Large White) were randomly divided into four groups (2 pigs per group) and were immunized twice at 0 and 28 days with infectious rSPV-SA (1 × 10 8 PFU/ml in 2 ml of PBS), inactivated-TGEV (1 × 10 8 PFU/ml in 2 ml of PBS), wtSPV (1 × 10 8 PFU/ml in 2 ml of PBS) or PBS, each time via three routes: oral, nasal, and intraperitoneal. To explore whether mice or swine generated TGEV neutralizing antibodies, serum from the PBS, wtSPV, inactivated-TGEV and rSPV-SA treated mice and pig were collected at 0, 14, 21, 35, 42 days post-primary immunization (1:100-1:12,800 dilution in a 100 l volume).

title:
  Efficacy and immunogenicity of recombinant swinepox virus expressing the A epitope of the TGEV S protein

abstract:
  To explore the possibility of developing a vaccine against transmissible gastroenteritis virus (TGEV) infection, a recombinant swinepox virus (rSPV-SA) expressing a TGEV protective antigen has been constructed. Immune responses and protection efficacy of the vaccination vector were assessed in both mice and pig models. An indirect ELISA assay suggested that when mice were vaccinated with rSPV-SA, the level of IgG against TGEV was enhanced dramatically. The cytokine assays were employed and the results indicated that both the Th1-type and Th2-type cytokine levels raised after vaccination with rSPV-SA in mice models. Results from the passive immunity protection test of new born piglets demonstrated that the recombinant live-vector vaccine, rSPV-SA, could 100% protect piglets from the SPV infection, and there was no significant clinical symptom in the rSPV-SA treatment group during this experiment. The data suggest that the novel recombinant swinepox virus is a potential vaccine against TGEV infection.


id: cord-276009-p98wjtjb
author: Iyer, Arun V.
date: 2009-02-05
txt: ./txt/cord-276009-p98wjtjb.txt
cache: ./cache/cord-276009-p98wjtjb.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/19070640/
doi: 10.1016/j.vaccine.2008.11.087
summary:
  title: Recombinant vesicular stomatitis virus-based west Nile vaccine elicits strong humoral and cellular immune responses and protects mice against lethal challenge with the virulent west Nile virus strain LSU-AR01 These results suggest that VSV-vectored vaccines administered intranasally can efficiently induce protective humoral and cellular immune responses against WNV infections. The salient features of this vaccine study are: (1) A prime-boost intranasal vaccination approach with recombinant VSVs expressing the WNV E glycoprotein produced robust CD8 + IFN␥ + T cell responses; (2) This vaccine approach produced strong neutralizing titers against the WNV; (3) Vaccinated mice were protected against lethal challenge and they were free of neuronal necrosis, while unvaccinated mice There was no statistically significant difference observed between these two groups. These results suggest that a prime-boost VSV-vectored intranasal vaccine approach induces strong humoral and cellular immune responses that protect mice against WNV-induced neuronal necrosis.

title:
  Recombinant vesicular stomatitis virus-based west Nile vaccine elicits strong humoral and cellular immune responses and protects mice against lethal challenge with the virulent west Nile virus strain LSU-AR01

abstract:
  Vesicular stomatitis virus (VSV) has been extensively utilized as a viral vector system for the induction of protective immune responses against a variety of pathogens. We constructed recombinant VSVs specifying either the Indiana or Chandipura virus G glycoprotein and expressing the West Nile virus (WNV) envelope (E) glycoprotein. Mice were intranasally vaccinated using a prime (Indiana)-boost (Chandipura) immunization approach and challenged with the virulent WNV-LSU-AR01. Ninety-percent (9 of 10) of the vaccinated mice survived as compared to 10% of the mock-vaccinated mice after WNV lethal challenge. Histopathological examination of brain tissues revealed neuronal necrosis in mock-vaccinated mice but not in vaccinated mice, and vaccinated, but not mock-vaccinated mice developed a strong neutralizing antibody response against WNV. Extensive immunological analysis using polychromatic flow cytometry staining revealed that vaccinated, but not mock-vaccinated mice developed robust cellular immune responses as evidenced by up-regulation of CD4(+) CD154(+) IFNγ(+) T cells in vaccinated, but not mock-vaccinated mice. Similarly, vaccinated mice developed robust E-glycoprotein-specific CD8(+) T cell immune responses as evidenced by the presence of a high percentage of CD8(+) CD62L(low) IFNγ(+) cells. In addition, a sizeable population of CD8(+) CD69(+) cells was detected indicating E-specific activation of mature T cells and CD4(+) CD25(+) CD127(low) T regulatory (T reg) cells were down-regulated. These results suggest that VSV-vectored vaccines administered intranasally can efficiently induce protective humoral and cellular immune responses against WNV infections.


id: cord-276209-5999g9gp
title: Tortoises, hares, and vaccines: A cautionary note for SARS-CoV-2 vaccine development
author: Poland, Gregory A.
date: 2020-06-02
txt: ./txt/cord-276209-5999g9gp.txt
cache: ./cache/cord-276209-5999g9gp.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1016/j.vaccine.2020.04.073
doi: 10.1016/j.vaccine.2020.04.073
abstract: nan
summary:
  Very soon thereafter, the causative agent was identified as the now-named SARS-CoV-2 virus-a betacoronavirus that had crossed the species barrier to infect humans. There is no question that a vaccine against this virus, and other as-yet-to-come coronaviruses, is imperative to protect human health and to quickly respond to future viral introductions, epidemics, and pandemics. These pathways, informed by science and the past history of successes and failures, are designed to maximize the chances of efficacy and safety. Further mutations could conceivably lead to issues of original antigenic sin with resultant disease enhancement after exposure or to vaccines that simply are not effective into the future. In addition to safety issues, I raise concern over ''''S-only" vaccine approaches for the mid-to long-term control of this RNA virus. We need a vaccine-and we need it as quickly as one can be developed-that demonstrates safety and efficacy in adequately powered studies.


id: cord-276907-b855tj7x
author: Giersing, Birgitte K.
date: 2019-11-28
txt: ./txt/cord-276907-b855tj7x.txt
cache: ./cache/cord-276907-b855tj7x.txt
extension: .txt
mime: text/plain
url: https://www.sciencedirect.com/science/article/pii/S0264410X16312051
doi: 10.1016/j.vaccine.2016.10.090
summary:
  Fortunately, at the current time, development of a norovirus vaccine that may offer efficacy in the context of low and middle income countries is proceeding with investment from the private sector, however an assessment of vaccine programmatic suitability and applicability to prequalification is needed, prior to Phase III trials to ensure the vaccine is appropriate for use in LMICs, assuming it is demonstrated to offer coverage over circulating genotypes within LMICs. Rotavirus is the leading cause of severe diarrhea among all children below 5 years of age worldwide, causing 20-40% of severe diarrheal hospitalisations, and is associated with significant mortality, with the latest mortality estimates at 215,000 deaths in 2013 [24] .

title:
  Report from the World Health Organization’s third Product Development for Vaccines Advisory Committee (PDVAC) meeting, Geneva, 8–10th June 2016

abstract:
  Abstract The third meeting of WHO’s Product Development for Vaccines Advisory Committee (PDVAC) was held in June 2016, with a remit to revisit the pathogen areas for which significant progress has occurred since recommendations from the 2015 meeting, as well as to consider new advances in the development of vaccines against other pathogens. Since the previous meeting, significant progress has been made with regulatory approvals of the first malaria and dengue vaccines, and the first phase III trials of a respiratory syncytial virus (RSV) vaccine candidate has started in the elderly and pregnant women. In addition, PDVAC has also supported vaccine development efforts against important emerging pathogens, including Middle Eastern Coronavirus (MERS CoV) and Zika virus. Trials of HIV and tuberculosis vaccine candidates are steadily progressing towards pivotal data points, and the leading norovirus vaccine candidate has entered a phase IIb efficacy study. WHO’s Immunization, Vaccine and Biologicals (IVB) department is actively working in several pathogen areas on the recommendation of PDVAC, as well as continuing horizon scanning for advances in the development of vaccines that may benefit low and middle income countries (LMICs), such as the recent licensure of the enterovirus 71 (EV71) vaccine in China. Following on from discussions with WHO’s Strategic Advisory Group of Experts (SAGE) on Immunization, PDVAC will also look beyond licensure and consider data needs for vaccine recommendation and implementation to reduce the delay between vaccine approval and vaccine impact.


id: cord-277054-eq4obbte
author: Kaur, Manpreet
date: 2009-03-26
url: https://www.sciencedirect.com/science/article/pii/S0264410X0900200X
doi: 10.1016/j.vaccine.2009.01.128
title:
  Rabies DNA vaccine: No impact of MHC Class I and Class II targeting sequences on immune response and protection against lethal challenge

abstract:
  Rabies is progressive fatal encephalitis. WHO estimates 55,000 rabies deaths and more than 10 million PEP every year world-wide. A variety of cell-culture derived vaccines are available for prophylaxis against rabies. However, their high cost restricts their usage in developing countries, where such cases are most often encountered. This is driving the quest for newer vaccine formulations; DNA vaccines being most promising amongst them. Here, we explored strategies of antigen trafficking to various cellular compartments aiming at improving both humoral and cellular immunity. These strategies include use of signal sequences namely Tissue Plasminogen Activator (TPA), Ubiquitin (UQ) and Lysosomal-Associated Membrane Protein-1 (LAMP-1). TPA, LAMP-1 and their combination were aimed at enhancing the CD4(+) T cell and antibody response. In contrast, the UQ tag was utilized for enhancing CD8(+) response. The potency of modified DNA vaccines assessed by total antibody response, antibody isotypes, cytokine profile, neutralizing antibody titer and protection conferred against in vivo challenge; was enhanced in comparison to native unmodified vaccine, but the response elicited did not pertain to the type of target sequence and the directed arm of immunity. Interestingly, the DNA vaccines that had been designed to generate different type of immune responses yielded in effect similar response. In conclusion, our data indicate that the directing target sequence is not the exclusive deciding factor for type and extent of immune response elicited and emphasizes on the antigen dependence of immune enhancement strategies.


id: cord-277355-si3g5dih
title: The role of capsid in the flaviviral life cycle and perspectives for vaccine development
author: He, Yu
date: 2020-09-17
txt: ./txt/cord-277355-si3g5dih.txt
cache: ./cache/cord-277355-si3g5dih.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1016/j.vaccine.2020.08.053
doi: 10.1016/j.vaccine.2020.08.053
summary:
  Although current studies on flaviviruses have shown that the flaviviral assembly process does not exhibit a necessary step occurring in the cell nucleus, it has been well demonstrated that many mosquito-borne flavivirus CPs partially localize in the cell nucleus [44] [45] [46] [47] [48] ; in the cytoplasm, in addition to localizing in the ER, DENV CP and ZIKV CP have also been demonstrated to accumulate on LDs [13, 16] , but the link between the functional importance and the subcellular distribution of CPs is still unclear. Interestingly, a study showed that a CD61-71 mutant had abolished ZIKV infectious virion production that was then restored by adaptive mutations (prM-E21K and NS2B-E27G) only in BHK21 cells but not in other cell lines (indicate complex interactions that apparently occur between structural and non-structural proteins during virus replication and/or assembly), making this live virus function like a single-round infectious particle (SRIP) in vivo and safely inducing strong immunity protection against vertical transmission in mice [33] .

abstract:
  The arthropod-borne flaviviruses cause a series of diseases in humans and pose a significant threat to global public health. In this review, we aimed to summarize the structure of the capsid protein (CP), its relevant multiple functions in the viral life cycle and innovative vaccines targeting CP. The flaviviral CP is the smallest structural protein and forms a homodimer by antiparallel α-helixes. Its primary function is to package the genomic RNA; however, both steps of assembly and dissociation of nucleocapsid complexes (NCs) have been obscure until now; in fact, flaviviral budding is NC-free, demonstrated by the subviral particles that generally exist in flavivirus infection. In infected cells, CPs associate with lipid droplets, which possibly store CPs prior to packaging. However, the function of nuclear localization of CPs remains unknown. Moreover, introducing deletions into CPs can be used to rationally design safe and effective live-attenuated vaccines or noninfectious replicon vaccines and single-round infectious particles, the latter two representing promising approaches for innovative flaviviral vaccine development.


id: cord-278598-3utk3k6z
title: Safety and efficacy of an infectious bronchitis virus used for chicken embryo vaccination
author: Tarpey, I.
date: 2006-11-17
txt: ./txt/cord-278598-3utk3k6z.txt
cache: ./cache/cord-278598-3utk3k6z.txt
extension: .txt
mime: text/plain
url: https://www.sciencedirect.com/science/article/pii/S0264410X06007687
doi: 10.1016/j.vaccine.2006.06.040
summary:
  Recombinant IBVs based on the Beaudette strain expressing the Beaudette spike protein (Beau-R) or that from the virulent M41 strain (BeauR-M41(S)) were assessed for their potential as prototype vaccines for application to 18-day-old embryos. In Experiment 1, three birds from the CV1-vaccinated groups and five in each of Beau-R and BeauR-M41(S) in ovo-vaccinated groups were euthanized 6 days post hatch and their ciliary activity assessed. In Experiment 2 (vaccination dose for the Beaudette-based viruses was 10 4 EID 50 ) birds were challenged at 6 weeks post hatch with virulent M41 virus and the ciliary activity tested on days 5 and 7 post challenge (Fig. 4B) . In Experiment 2 (vaccination dose for the Beaudette-based viruses was 10 4 EID 50 ) birds were challenged at 6 weeks post hatch with virulent M41 virus and the ciliary activity tested on days 5 and 7 post challenge (Fig. 4B) .

abstract:
  Commercial vaccines for in ovo vaccination have not yet been developed for infectious bronchitis virus (IBV), the major coronavirus in the poultry industry. Recombinant IBVs based on the Beaudette strain expressing the Beaudette spike protein (Beau-R) or that from the virulent M41 strain (BeauR-M41(S)) were assessed for their potential as prototype vaccines for application to 18-day-old embryos. Pathogenicity was assessed by observing the effect on hatchability, and/or the production of nasal discharge and/or the effects on ciliary activity in the trachea at various time points post hatch. In contrast to commercial IBV vaccines given in ovo, the Beau-R and BeauR-M41(S) strains did not reduce hatchability or cause nasal discharge, and caused minimal damage to the ciliated epithelium of the trachea. The presence of the spike protein from a virulent virus did not increase the pathogenicity of the virus according to the criteria used. Assessment of the BeauR-M41(S) strain for efficacy showed that it protected up to 90% of chicks against challenge with virulent IB virus (M41) in a dose dependent manner. Further egg passage of the BeauR-M41(S) strain (BeauR-M41(S) EP10) did not increase its pathogenicity though it did improve its efficacy, based on serology and protection against a virulent challenge. BeauR-M41(S) EP10 was more efficacious than BeauR-M41(S) protecting more birds against virulent challenge and providing a better serological antibody response. BeauR-M41(S) EP10 induced a serological response similar to that of a commercial vaccine given at day-old though the commercial vaccine provided slightly higher efficacy. These results are promising for the development of embryo safe efficacious IBV vaccines for in ovo application.


id: cord-279364-j93f6eso
author: Liao, Qiuyan
date: 2020-05-07
txt: ./txt/cord-279364-j93f6eso.txt
cache: ./cache/cord-279364-j93f6eso.txt
extension: .txt
mime: text/plain
url: https://www.sciencedirect.com/science/article/pii/S0264410X20306307
doi: 10.1016/j.vaccine.2020.05.012
summary:
  The DCE was designed to examine the relative importance of vaccine characteristics (vaccine efficacy and safety), social normative influence reflected by the proportion of HCP colleagues intending to take SIV, and convenience in access to vaccine indicated by vaccination programme duration, vaccination location, vaccination arrangement procedure and service hours in determining influenza vaccination choice among HCP.

title:
  What influenza vaccination programmes are preferred by healthcare personnel? A discrete choice experiment

abstract:
  OBJECTIVES: This study examined the relative importance of factors relating to vaccine characteristics, social normative influence and convenience in access to vaccine for determining decision making for seasonal influenza vaccination (SIV) among healthcare personnel (HCP), aiming to optimize existing influenza vaccination programmes for HCP. METHODS: A discrete choice experiment (DCE) was conducted in HCP working in public hospitals in Hong Kong. The DCE was designed to examine the relative importance of vaccine characteristics (vaccine efficacy and safety), social normative influence reflected by the proportion of HCP colleagues intending to take SIV, and convenience in access to vaccine indicated by vaccination programme duration, vaccination location, vaccination arrangement procedure and service hours in determining influenza vaccination choice among HCP. Mixed logit regression modelling was conducted to examine the preference weight (β) of factors included in the DCE for determining vaccination choice. RESULTS: Vaccination probability increased with increase in vaccine efficacy (β = 0.02 for per 1% increase), vaccination location changing from “designated staff clinic” to “mobile station” (β = 0.37), vaccination arrangement procedure changing from “by appointment” to “by walk-in” (β = 0.99), but decreased with the increase in probability of mild reactions to vaccination (β = −0.05 for per 1% increase). CONCLUSION: Vaccine safety was judged to be more important than vaccine efficacy for determining vaccination choice. Arranging vaccination service by walk-in and implementing mobile vaccination station should be considered in future SIV programmes to compensate for the effect of perceived low vaccination efficacy and concerns about vaccine safety to promote SIV uptake among HCP.


id: cord-279841-oq25o4qr
title: Viral and host determinants of RNA virus vector replication and expression
author: Ahlquist, Paul
date: 2005-03-07
url: https://www.ncbi.nlm.nih.gov/pubmed/15734041/
doi: 10.1016/j.vaccine.2004.11.005
abstract:
  Positive-strand RNA viruses have proven to be valuable vectors for delivery and expression of antigens for direct vaccination of animals and vaccine production in plants. However, optimal use of these viruses as vectors for vaccine and other purposes is limited by incomplete understanding of their replication pathways and associated constraints on inserted foreign genes. Further insights into RNA virus vector design and optimization are emerging from recent advances on the function of viral RNA replication factors, the nature of the viral RNA replication complex as a membrane-bounded compartment sequestering replication components from competing processes and host defenses, and identification of surprisingly diverse host genes contributing to many virus replication steps.


id: cord-279985-de0b27nq
title: Kunjin replicon-based simian immunodeficiency virus gag vaccines
author: Anraku, Itaru
date: 2008-06-19
txt: ./txt/cord-279985-de0b27nq.txt
cache: ./cache/cord-279985-de0b27nq.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1016/j.vaccine.2008.04.001
doi: 10.1016/j.vaccine.2008.04.001
summary:
  Kunjin replicon VLP vaccines encoding HIV-1 gag have also been shown to induce CD8 T cell immunity comparable to that seen after immunisation with recombinant vaccinia [11] . Here we describe the behaviour of four different Kunjin replicon VLP vaccines encoding SIV gag and show that only the Gag-pol vaccine (i) induced good levels of both effector memory and central memory T cell responses 10 weeks post-vaccination, comparable to those induced by the previously described HIV-1 gag Kunjin replicon VLP vaccine [11] , (ii) showed good levels of protection against challenge with A20 cells expressing SIV Gag ≈9 months post-vaccination, and (iii) displayed high levels of insert stability. In summary we describe here a Kunjin replicon SIV Gag-pol VLP vaccine, which showed high insert stability, good induction of effector and central memory responses, and good protection against a model challenge.

abstract:
  An RNA-based, non-cytopathic replicon vector system, based on the flavivirus Kunjin, has shown considerable promise as a new vaccine delivery system. Here we describe the testing in mice of four different SIVmac239 gag vaccines delivered by Kunjin replicon virus-like-particles. The four vaccines encoded the wild type gag gene, an RNA-optimised gag gene, a codon-optimised gag gene and a modified gag-pol gene construct. The vaccines behaved quite differently for induction of effector memory and central memory responses, for mediation of protection, and with respect to insert stability, with the SIV gag-pol vaccine providing the optimal performance. These results illustrate that for an RNA-based vector the RNA sequence of the antigen can have profound and unforeseen consequences on vaccine behaviour.


id: cord-281635-a6ia8kxf
author: Bellinzoni, R. C.
date: 1989-06-30
txt: ./txt/cord-281635-a6ia8kxf.txt
cache: ./cache/cord-281635-a6ia8kxf.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/2551102/
doi: 10.1016/0264-410x(89)90241-7
summary:
  title: Efficacy of an inactivated oil-adjuvanted rotavirus vaccine in the control of calf diarrhoea in beef herds in Argentina In a small-scale experimental trial, involving 21 pregnant cows (13 vaccinated and eight unvaccinated controls), a significant increase in neutralizing antibody titres against different serotypes of bovine rotaviruses was found in both the colostrum and serum of vaccinated cows compared with that of unvaccinated controls. For that reason, after several years of epidemiological studies, it was decided to develop and test an inactivated oil-adjuvanted vaccine with the aim of controlling diarrhoea in beef and dairy herds in Argentina. The results showed that the oil-adjuvanted rotavirus vaccine tested was effective in the control of calf neonatal diarrhoea in Argentina. As shown in Figure 1 , compared with controls, vaccinated cows showed significantly higher neutralizing antibody levels against rotavirus in serum, colostrum and milk until at least 30 days after calving.

title:
  Efficacy of an inactivated oil-adjuvanted rotavirus vaccine in the control of calf diarrhoea in beef herds in Argentina

abstract:
  Abstract We have assessed the potency of an inactivated oil-adjuvanted rotavirus vaccine in beef herds in Argentina. Two different vaccine trials were conducted. In a small-scale experimental trial, involving 21 pregnant cows (13 vaccinated and eight unvaccinated controls), a significant increase in neutralizing antibody titres against different serotypes of bovine rotaviruses was found in both the colostrum and serum of vaccinated cows compared with that of unvaccinated controls. Seven days after birth, half of the calves born to vaccinated dams or to control cows were challenged with live virulent virus whereas the other half of both groups were left in contact with the infected calves in order to mimic a natural field challenge. Although no statistically significant differences in the rate of protection were observed among the different groups of animals, a larger number of vaccinated calves were protected in comparison with their controls, particularly where animals in contact with infected calves were concerned. Secondly, a large-scale field trial was carried out in 17 beef herds involving a total of 4066 vaccinated pregnant cows. In 11 farms morbidity and mortality in calves from vaccinated cows were compared with historical data from the previous 3 years at the same locations. In the other six herds, control groups were used to compare data of the same year: 1540 cows were vaccinated and 2700 were left as controls. Taking into account the previous and current incidence of diarrhoea, morbidity and mortality were significantly reduced in 16 of the 17 beef herds tested. Vaccine effectiveness was also evident in farms where other enteropathogens such as cryptosporidium and coronaviruses were present, together with rotavirus.


id: cord-281676-yy5etfek
author: Dwivedi, Varun
date: 2011-05-23
txt: ./txt/cord-281676-yy5etfek.txt
cache: ./cache/cord-281676-yy5etfek.txt
extension: .txt
mime: text/plain
url: https://www.sciencedirect.com/science/article/pii/S0264410X11003586
doi: 10.1016/j.vaccine.2011.03.006
summary:
  Consistent with the reduced lung lesions and viremia, a significantly increased frequency of IFN-␥Table 1 Frequency of immune cells in pigs inoculated intranasally with mock (no vaccination and no challenge), unvaccinated (n = 9) or vaccinated with PRRS-MLV+ Mtb WCL (n = 9) and then challenged with PRRSV MN184. Evaluation of the frequency of various immune cells at both mucosal (lung and TBLN MNC) and systemic sites (PBMC) in vaccinated and virulent PRRSV challenged pigs is important for associating cytokine responses. In our study, a consistently reduced frequency of Tregs in the lungs, blood, and TBLN of pigs vaccinated intranasally with PRRS-MLV+ Mtb WCL was detected which was associated with reduced secretion of both the immunosuppressive cytokines, IL-10 and TGF-␤. 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

title:
  Cross-protective immunity to porcine reproductive and respiratory syndrome virus by intranasal delivery of a live virus vaccine with a potent adjuvant

abstract:
  Abstract Porcine reproductive and respiratory syndrome (PRRS) is an immunosuppressive chronic respiratory viral disease of pigs that is responsible for major economic losses to the swine industry worldwide. The efficacy of parenteral administration of widely used modified live virus PRRS vaccine (PRRS-MLV) against genetically divergent PRRSV strains remains questionable. Therefore, we evaluated an alternate and proven mucosal immunization approach by intranasal delivery of PRRS-MLV (strain VR2332) with a potent adjuvant to elicit cross-protective immunity against a heterologous PRRSV (strain MN184). Mycobacterium tuberculosis whole cell lysate (Mtb WCL) was chosen as a potent mucosal adjuvant due to its Th1 biased immune response to PRRS-MLV. Unvaccinated pigs challenged with MN184 had clinical PRRS with severe lung pathology; however, vaccinated (PRRS-MLV+ Mtb WCL) pigs challenged with MN184 were apparently healthy. There was a significant increase in the body weight gain in vaccinated compared to unvaccinated PRRSV challenged pigs. Vaccinated compared to unvaccinated, virus-challenged pigs had reduced lung pathology associated with enhanced PRRSV neutralizing antibody titers and reduced viremia. Immunologically, an increased frequency of Th cells, Th/memory cells, γδ T cells, dendritic cells, and activated Th cells and a reduced frequency of T-regulatory cells were detected at both mucosal and systemic sites. Further, reduced secretion of immunosuppressive cytokines (IL-10 and TGF-β) and upregulation of the Th1 cytokine IFN-γ in blood and lungs were detected in mucosally vaccinated, PRRSV-challenged pigs. In conclusion, intranasal immunization of pigs with PRRS-MLV administered with Mtb WCL generated effective cross-protective immunity against PRRSV.


id: cord-282158-08u3x1z4
author: Yang, William H.
date: 2013-09-13
txt: ./txt/cord-282158-08u3x1z4.txt
cache: ./cache/cord-282158-08u3x1z4.txt
extension: .txt
mime: text/plain
url: https://www.sciencedirect.com/science/article/pii/S0264410X13009286
doi: 10.1016/j.vaccine.2013.07.007
summary:
  This large-scale, randomized study in subjects ≥18 years of age assessed whether one dose of AS03-adjuvanted 3.75 g HA influenza A(H1N1)pdm09 vaccine elicited immune response that met the US and European regulatory criteria. A single dose of the AS03-adjuvanted 3.75 g HA influenza A(H1N1)pdm09 vaccine elicited HI immune responses in the 18-64 years and >64 years age groups that met the CBER regulatory criteria at Day 21 ( Table 1 ). At Day 21, a single dose of the non-adjuvanted 15 g HA influenza A(H1N1)pdm09 vaccine elicited HI immune responses in subjects 18-64 years and >64 years of age that met the CBER regulatory criteria (Table 1) . Data from this large, controlled study in adults 18 years of age and older demonstrated that a single dose of AS03-adjuvanted or non-adjuvanted influenza A(H1N1)pdm09 vaccine elicited strong HI immune responses 21 days later that met the CHMP and the more stringent CBER criteria for pandemic influenza vaccines.

title:
  Long-term immunogenicity of an AS03-adjuvanted influenza A(H1N1)pdm09 vaccine in young and elderly adults: An observer-blind, randomized trial()

abstract:
  BACKGROUND: This study (NCT00979602) evaluated the immunogenicity and relative protective efficacy of one dose of influenza A(H1N1)pdm09 vaccine with or without AS03 (an α-tocopherol oil-in-water emulsion based Adjuvant System). METHODS: Four thousands and forty-eight healthy adults aged ≥18 years were randomized (1:1) to receive one dose of either the adjuvanted split virion (3.75 μg hemagglutinin antigen [HA]/AS03) or non-adjuvanted (15 μg HA) vaccine. Hemagglutination inhibition [HI] antibody response was evaluated before vaccination and at Days 21, 42 and 182 (Month 6). Safety of the study vaccines was evaluated during the entire study duration. RESULTS: At Day 21, both study vaccines induced HI immune responses meeting the US regulatory criteria in subjects 18–64 years (seroprotection rate [SPR]: 98.0% [97.1–98.6]; seroconversion rate [SCR]: 89.7% [88.0–91.2] in the AS03-adjuvanted group; SPR: 91.4% [89.9–92.8]; SCR: 74.6% [72.3–76.9] in the non-adjuvanted group) and >64 years of age (SPR: 86.0% [82.5–89.0]; SCR: 75.3% [71.1–79.2] in the AS03-adjuvanted group; SPR: 69.1% [64.6–73.3]; SCR: 56.7% [52.0–61.3] in the non-adjuvanted group). The AS03-adjuvanted vaccine induced higher HI geometric mean titers than the non-adjuvanted vaccine at all time points. At Month 6, only subjects 18–64 years of age from both vaccine groups still met the US regulatory criteria (SPR: 82.1% [80.0–84.1]; SCR: 62.3% [59.6–64.8] in the AS03-adjuvanted group; SPR: 75.3% [72.9–77.5]; SCR: 53.7% [51.0–56.4] in the non-adjuvanted group). Protective efficacy was not evaluated due to low number of RT-qPCR-confirmed A(H1N1)pdm09 influenza cases. Through Month 12, 216 serious adverse events (in 157 subjects: 84 in the AS03-adjuvanted and 73 in the non-adjuvanted group) and 12 potentially immune mediated diseases (5 in the AS03-adjuvanted and 7 in the non-adjuvanted group) were reported. CONCLUSION: A single dose of either adjuvanted or non-adjuvanted influenza A(H1N1)pdm09 vaccine induced protective HI antibody levels against the A/California/7/2009 strain that persisted through Month 6 in the 18–64 years population.


id: cord-282314-9cua2jzg
author: Albanese, Grace A.
date: 2018-10-01
txt: ./txt/cord-282314-9cua2jzg.txt
cache: ./cache/cord-282314-9cua2jzg.txt
extension: .txt
mime: text/plain
url: https://www.sciencedirect.com/science/article/pii/S0264410X18312283
doi: 10.1016/j.vaccine.2018.08.078
summary:
  Abbreviations: Ark99, Arkansas 99; ArkDPI, Arkansas Delmarva Poultry Industry; ArkGA, Arkansas Georgia; CAS, chorioallantoic sac; C T , cycle threshold; EID 50 , 50% embryo infective dose; IBV, infectious bronchitis virus; MHV, murine hepatitis virus; nsp2, nonstructural protein 2; nsp3, nonstructural protein 3; P, passage; PBS, phosphate-buffered saline; qRT-PCR, quantitative real-time reverse-transcriptase polymerase chain reaction; RT-PCR, reverse-transcriptase polymerase chain reaction; SARS-CoV, severe acute respiratory syndrome coronavirus; SD, standard deviation; SEM, standard error of mean; SNP, single nucleotide polymorphism; SPF, specific-pathogen free; US, United States; USDA, United States Department of Agriculture. In P60, SNPs were seen in S1 as well as S2 of the Table 2 S1 amino acid sequence comparison of ArkGA vaccine virus and viral RNA isolated from 5 choanal cleft palate swabs on days 7, 10, and 14 post-vaccination.

title:
  Biological and molecular characterization of ArkGA: A novel Arkansas serotype vaccine that is highly attenuated, efficacious, and protective against homologous challenge

abstract:
  Almost all commercial poultry are vaccinated against avian coronavirus infectious bronchitis virus (IBV) using live attenuated vaccines mass administered by spray at day of hatch. Although many different types of IBV vaccines are used successfully, the ArkDPI serotype vaccine, when applied by spray, does not infect and replicate sufficiently to provide protection against homologous challenge. In this study, we examined a different Ark vaccine strain (Ark99), which is no longer used commercially due to its reactivity in one day old chicks, to determine if it could be further attenuated by passage in embryonated eggs but still provide adequate protection. Further attenuation of the Ark99 vaccine was achieved by passage in embryonated eggs but ArkGA P1, P20, and P40 (designated ArkGA after P1) were still too reactive to be suitable vaccine candidates. However, ArkGA P60 when given by spray had little or no vaccine reaction in one day old broiler chicks, and it induced protection from clinical signs and ciliostasis following homologous challenge. In addition, vaccinated and challenged birds had significantly less challenge virus, an important measure of protection, compared to non-vaccinated and challenged controls. The full-length genomes of viruses from egg passages 1, 20, 40, and 60 were sequenced using the Illumina platform and the data showed single nucleotide polymorphisms (SNPs) had accumulated in regions of the genome associated with viral replication, pathogenicity, and cell tropism. ArkGA P60 accumulated the most SNPs in key genes associated with pathogenicity (polyprotein gene 1ab) and cell tropism (spike gene), compared to previous passages, which likely resulted in its more attenuated phenotype. These results indicate that the ArkGA P60 vaccine is safe for spray vaccination of broiler chicks and induces suitable protection against challenge with pathogenic Ark-type virus.


id: cord-282764-d9x1wii6
author: Chang, Chia-Yin
date: 2006-02-20
txt: ./txt/cord-282764-d9x1wii6.txt
cache: ./cache/cord-282764-d9x1wii6.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/16194584/
doi: 10.1016/j.vaccine.2005.09.011
summary:
  title: Influence of intron and exon splicing enhancers on mammalian cell expression of a truncated spike protein of SARS-CoV and its implication for subunit vaccine development A truncated S protein of the TW1 strain, S(TR2) (88 kDa), carrying three S fragments (S74–253, S294–739, and S1129–1255) was investigated to study the influences of intron and exon splicing enhancers to improve S(TR2) protein expression in mammalian cells. Therefore, several different strategies for improving S TR2 protein expression in mammalian cells were investigated in this report, including intron addition and the application of exon splicing enhancers. The intron-dependent enhancement of S TR2 protein expression in CHO/dhFr− cells was further investigated by measuring total RNA level, in vivo RNA stability, and RNA elongation rate in this study. The results indicated that the intron-dependent S TR2 protein expression in mammalian cells correlated with a higher level of total RNA accumulation as determined by quantitative RT-PCR (Fig. 4A) .

title:
  Influence of intron and exon splicing enhancers on mammalian cell expression of a truncated spike protein of SARS-CoV and its implication for subunit vaccine development

abstract:
  The spike (S) protein of severe acute respiratory syndrome coronavirus (SARS-CoV) is important for vaccine development. A truncated S protein of the TW1 strain, S(TR2) (88 kDa), carrying three S fragments (S74–253, S294–739, and S1129–1255) was investigated to study the influences of intron and exon splicing enhancers to improve S(TR2) protein expression in mammalian cells. Our results showed that S(TR2) protein expression with the use of an 138 base-pair intron addition increased by 1.9-, 2.5-, and 4.1-fold in Vero E6, QBI-293A cells, and CHO/dhFr− cells (dihydrofolate reductase [dhfr] gene deficient CHO cells), respectively. Using the exon splicing enhancers, including a bidirectional splicing enhancer (BSE) or an exon splicing enhancer derived from the EDA alternative exon of the fibronectin gene (EDA ESE), were also found to increase S(TR2) protein expression in CHO/dhFr− cells by 1.7- and 2.6-fold. Nevertheless, combination of the intron and the exon splicing enhancers resulted in suppressing the intron-enhancing e S(TR2) protein expression in in CHO/dhFr− cells. Our studies also demonstrated the S(TR2) protein was mainly as the Endo H-sensitive glycoprotein (115 kDa) expressed in Vero E6, QBI-293A, and CHO/dhFr− cells. However, only a minor form of the Endo H-resistant glycoproteins (∼130 kDa) was detected in CHO/dhFr− cells. Taken together, our results indicated that intron had a better enhancing effect on S(TR2) protein expression than exon splicing enhancers, and the expression of ∼130 kDa S(TR2) glycoprotein was enhanced by the intron addition into the expression vector construct. Results of the present study can provide an optimal strategy to enhance SARS-CoV S protein expression in mammalian cells and may contribute to the development of SARS-CoV subunit vaccine.


id: cord-283475-28900qlr
title: Vaccine-preventable disease control in the People’s Republic of China: 1949–2016
author: Yu, Wenzhou
date: 2018-12-18
txt: ./txt/cord-283475-28900qlr.txt
cache: ./cache/cord-283475-28900qlr.txt
extension: .txt
mime: text/plain
url: https://api.elsevier.com/content/article/pii/S0264410X18313574
doi: 10.1016/j.vaccine.2018.10.005
summary:
  Vaccine production was increased and the frequency of campaigns were increased with most provinces conducting at least two or three province-wide campaigns each year; live vaccines in the fall and winter and killed In support of the 1985 United Nations resolution on Universal Childhood Immunization (UCI), ''''85-85" coverage goals were included in China''s ''''7th 5-year Plan for National Social and Economic Development, 1986-1990" setting targets of 85% percent coverage at province-level with BCG, DPT, OPV and measles by 12 months of age by 1988, and 85% coverage at county-level by 1990. In 1989, the National People''s Congress passed a law requiring health authorities at all levels implement a system of planned preventive immunizations that included issuing vaccination certificates to all children and establishing registers to monitor vaccination coverage at township levels and above.

abstract:
  BACKGROUND: China's immunization program is one of the oldest and largest in the world. Rates of vaccine-preventable diseases (VPD) are comparable to those in high-income countries. The program's evolution has been characterized by ambitious target setting and innovative strategies that have not been widely described. METHODS: We reviewed national and provincial health department archives; analyzed disease surveillance, vaccination coverage, and serosurvey data from 1950 through 2016; and, conducted in-depth interviews with senior Chinese experts involved early VPD control efforts. RESULTS: Widespread immunization began in the 1950s with smallpox, diphtheria, and Bacillus-Calmette Guerin vaccines, and in the 1960s with pertussis, tetanus, polio, measles, and Japanese encephalitis (JE) vaccines. The largest drops in absolute VPD burden occurred in the 1970s with establishment of the Rural Cooperative Medical System and a cadre of trained peasant health workers whose responsibilities included vaccinations. From 1970 to 1979, incidence per 100,000 population dropped 48% from 3.3 to 1.75 for diphtheria, 50% from 152.2 to 49.4 for pertussis, 77% from 2.5 to 0.6 for polio, 60% from 450.5 to 178.3 for measles, and 72% from 18.0 to 5.1 for JE, averting an average of 4 million VPD cases each year. Until the early 1980s, vaccines were delivered through annual winter campaigns using a coordinated ‘rush-relay’ system to expedite transport while leveraging vaccine thermostability. Establishment of the cold chain system during in the 1980s allowed bi-monthly vaccination rounds and more timely vaccination resulting in rates of diphtheria, pertussis, measles and meningitis falling over 90% from 1980 to 1989, while polio and JE rates fell 40–50%. In the 1990s, progress stalled as financing for public health was weakened by broad market reforms. Large investments in public health and immunizations by the central government since 2004 has led to further declines in VPD burden and increased equity. During 2011–2016, the incidence per 100,000 population was <2.0 for measles and <0.2 for pertussis, JE, meningococcal meningitis, and hepatitis A. From 1992 to 2014, the prevalence of chronic hepatitis B infection in children <5 years fell from 9.7% to 0.3%, a 97% decline. China was certified polio-free in 2000 and diphtheria was last reported in 2006. CONCLUSIONS: Long-term political commitment to immunizations as a basic right, ambitious targets, use of disease incidence as the primary metric to assess program performance, and nationwide scale-up of successful locally developed strategies that optimized use of available limited resources have been critical to China's success in controlling vaccine-preventable diseases.


id: cord-284882-8vil7k5l
author: MacDonald, Angus J.
date: 2005-05-16
txt: ./txt/cord-284882-8vil7k5l.txt
cache: ./cache/cord-284882-8vil7k5l.txt
extension: .txt
mime: text/plain
url: https://api.elsevier.com/content/article/pii/S0264410X05001489
doi: 10.1016/j.vaccine.2005.01.098
summary:
  title: rOv-ASP-1, a recombinant secreted protein of the helminth Onchocercavolvulus, is a potent adjuvant for inducing antibodies to ovalbumin, HIV-1 polypeptide and SARS-CoV peptide antigens After a single immunization and one boost, rOv-ASP-1 exceeded the efficacy of alum or MPL + TDM adjuvants in terms of end-point total IgG or IgG1 and IgG2a anti-OVA titres. While conducting experiments designed to evaluate recombinant Onchocerca volvulus ASP-1 (rOv-ASP-1) as a possible vaccine candidate against onchocerciasis in humans, we vaccinated mice with the recombinant protein alone or with alum or Freund''s adjuvants and measured IgG1 and IgG2a isotypes that are broadly associated with Th2 and Th1 T cell responses, respectively. Having shown that rOv-ASP-1 acted as a better adjuvant than alum or MPL + TDM in stimulating production of antibodies to OVA, we then tested if the protein had similar adjuvant potency for antigens derived from human pathogens, namely SARS-CoV and HIV-1.

title:
  rOv-ASP-1, a recombinant secreted protein of the helminth Onchocercavolvulus, is a potent adjuvant for inducing antibodies to ovalbumin, HIV-1 polypeptide and SARS-CoV peptide antigens

abstract:
  We studied the adjuvanticity of recombinant Onchocerca volvulus activation associated protein-1 (rOv-ASP-1) for ovalbumin (OVA) in mice. After a single immunization and one boost, rOv-ASP-1 exceeded the efficacy of alum or MPL + TDM adjuvants in terms of end-point total IgG or IgG1 and IgG2a anti-OVA titres. Using the helminth-derived adjuvant, IgG isotype responses to OVA were of a mixed Th1/Th2 profile and spleen cell cytokines exclusively Th1-type. The potent adjuvanticity of rOv-ASP-1 was confirmed in mice vaccinated with a 37-mer peptide from the S protein of SARS-CoV and an HIV-1 gp120-CD4 chimeric polypeptide antigen. Unusually for a helminth product, the rOv-ASP-1 adjuvant augmented not only Th2 but also Th1 responses, the latter property being of potential utility in stimulating anti-viral immune responses.


id: cord-285128-48l1w65p
author: Custers, Jerome
date: 2020-10-03
txt: ./txt/cord-285128-48l1w65p.txt
cache: ./cache/cord-285128-48l1w65p.txt
extension: .txt
mime: text/plain
url: https://www.sciencedirect.com/science/article/pii/S0264410X20311609?v=s5
doi: 10.1016/j.vaccine.2020.09.018
summary:
  A replication incompetent adenoviral vector based on human adenovirus type 26 (Ad26) has been evaluated in several clinical trials. Clinical trials have not shown meaningful impact of pre-existing immunity to Ad26 on vaccine immunogenicity, even in the presence of Ad26 neutralizing antibody titers or Ad26-targeting T cell responses at baseline. For example, a seroprevalence study of the 51 human adenovirus serotypes known at the time showed that several serotypes from particularly subgroups B and D, including Ad26, were rare in a Belgian population (3) , suggesting that vectors (rAd) derived from these serotypes might be useful alternatives to Ad5-based vectors for vaccine development, since for Ad5-based vectors it was shown that their high prevalence hampered their clinical use (4) (5) (6) (7) (8) . What is known about the effect of pre-existing immunity, including both natural immunity and repeat administration of the vector or the vaccine, on ''take'', safety or efficacy in any animal model or human studies using this vector?

title:
  Vaccines based on replication incompetent Ad26 viral vectors: standardized template with key considerations for a risk/benefit assessment

abstract:
  Replication-incompetent adenoviral vectors have been under investigation as a platform to carry a variety of transgenes, and express various antigens as a basis for preventive or therapeutic vaccine development. A replication incompetent adenoviral vector based on human adenovirus type 26 (Ad26) has been evaluated in several clinical trials. The Brighton Collaboration Viral Vector Vaccines Safety Working Group (V3SWG) was formed to evaluate the safety and features of recombinant viral vector vaccines. This paper reviews the biological features of the Ad26 vectors, including tabulation of safety and risk assessment characteristics of Ad26 vector-based vaccines. Substantial information on immunogenicity, clinical safety, biological characteristics and manufacturing are reported. In the Ad26 vector, deletion of the E1 gene, rendering the vector replication incompetent and providing space for transgene insertion, is combined with additional genetic engineering for vaccine manufacturability and transgene expression optimization. These vaccines are manufactured using the E1-complementing PER.C6® cell line, a continuous, human cell-line that can be cultured in serum-free medium in a suspension to high cell densities, providing an effective and flexible system for high-yield manufacturing. Ad26 vector vaccines have favorable thermostability profiles, compatible with vaccine supply chains. Safety data are compiled in the Ad26 vaccine safety database version 4.0, with unblinded data from 23 ongoing and completed clinical studies for a total of 3912 participants in Ebola, HIV, Malaria, RSV and Filovirus Ad26-based vaccine programs. Overall, all Ad26-based vaccines have been well tolerated, with no significant safety issues identified from the available data in the current Ad26 vaccine safety database. Evaluation of Ad26-based vaccines to further characterize the safety profile is continuing, with more than 90,000 participants vaccinated as of 1st July 2020 (cut-off date). Extensive evaluation of immunogenicity in humans shows strong and durable humoral and cellular immune responses. Clinical trials have not shown meaningful impact of pre-existing immunity to Ad26 on vaccine immunogenicity, even in the presence of Ad26 neutralizing antibody titers or Ad26-targeting T cell responses at baseline. The first vaccine, against Ebola virus, that makes use of the Ad26 vector, received marketing authorization from EC on 1st July 2020, as part of the Ad26.ZEBOV, MVA BN Filo vaccine regimen. New developments based on the Ad26 vector are underway, including a COVID-19 vaccine, which is currently in clinical evaluation.


id: cord-285613-hbd44euq
title: Vaccines in a hurry
author: Søborg, Christian
date: 2009-05-26
txt: ./txt/cord-285613-hbd44euq.txt
cache: ./cache/cord-285613-hbd44euq.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1016/j.vaccine.2009.02.030
doi: 10.1016/j.vaccine.2009.02.030
summary:
  Early recognition of an emerging microbial threat Identification and characterization of the causative agent Rapid understanding of natural history, pathogenesis, molecular biology and epidemiology; building on work in related pathogens as well as ongoing clinical, laboratory and epidemiological studies Identification of potential vaccine candidates Identification of potential delivery systems and suitable adjuvant to improve immunogenicity and sparing of antigen and dosages Production at pilot plant level Development and acceptance of correlates of immunity Development and acceptance of correlates of safety Limited trials in animals and humans based on these correlates as outcome measures Fast-track approval of the vaccines Enhancing production capacity by public-private partnerships Based on risk assessment and defined objectives: implementation of emergency vaccination Post-licensure follow-up of emergency vaccination with data accessible in real-time to medicine-and public health agencies as a surrogate for phase III trials and ensuring development with advance purchase agreements to establish a market.

abstract:
  Preparing populations for health threats, including threats from new or re-emerging infectious diseases is recognised as an important public health priority. The development, production and application of emergency vaccinations are the important measures against such threats. Vaccines are cost-effective tools to prevent disease, and emergency vaccines may be the only means to prevent a true disaster for global society in the event of a new pandemic with potential to cause morbidity and mortality comparable to the Spanish flu, the polio epidemics in the 1950s, or the SARS outbreak in 2003 if its spread had not been contained in time. Given the early recognition of a new threat, and given the advances of biotechnology, vaccinology and information systems, it is not an unrealistic goal to have promising prototype vaccine candidates available in a short time span following the identification of a new infectious agent; this is based on the assumption that the emerging infection is followed by natural immunity. However, major bottlenecks for the deployment of emergency vaccine are lack of established systems for fast-track regulatory approval of such candidates and limited international vaccine production capacity. In the present discussion paper, we propose mechanisms to facilitate development of emergency vaccines in Europe by focusing on public–private scientific partnerships, fast-track approval of emergency vaccine by regulatory agencies and proposing incentives for emergency vaccine production in private vaccine companies.


id: cord-288038-jdinf8od
author: Thindwa, Deus
date: 2020-06-19
txt: ./txt/cord-288038-jdinf8od.txt
cache: ./cache/cord-288038-jdinf8od.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/32600911/
doi: 10.1016/j.vaccine.2020.06.047
abstract: nan
summary:
  Vaccinating older adults at elevated risk of severe COVID-19 disease against vaccine preventable diseases may therefore not only help to reduce the strain on the healthcare system from those diseases during a pandemic, but also alleviate some of the potential COVID-19 mortality due to co-infecting pathogens [8] . Similarly, maintaining high vaccine coverage of existing PCV and live attenuated influenza vaccine programmes in children reduces the associated disease burden in older adults through herd effects, and will further enhance benefits for limiting COVID-19 risks. In summary, where already in routine use among older adults and/or adults at-risk, maintaining both seasonal influenza and PPV23 at high coverage have the potential to not only reduce the burden of the targeted diseases but also prevent a proportion of COVID-19 morbidity and mortality, if they can be delivered while minimising the risk for SARS-CoV-2 transmission.

title:
  Use of seasonal influenza and pneumococcal polysaccharide vaccines in older adults to reduce COVID-19 mortality


id: cord-288309-6pw7t512
author: Kusters, J. G.
date: 1990-12-31
txt: ./txt/cord-288309-6pw7t512.txt
cache: ./cache/cord-288309-6pw7t512.txt
extension: .txt
mime: text/plain
url: https://api.elsevier.com/content/article/pii/0264410X9090018H
doi: 10.1016/0264-410x(90)90018-h
summary:
  J.; Niesters, H.G.M.; van der Zeijst, B.A.M. title: Sequence evidence for RNA recombination in field isolates of avian coronavirus infectious bronchitis virus Nucleotide sequences of eight IBV isolates in a region of the genome suspected to contain recombination, were aligned and compared. To address the question of the frequency of recombination in the generation of new field isolates the nucleotide sequences in five windows of homologous sequences of the genomes of eight IBV strains have been compared. With the murine coronavirus MHV a high frequency of recombination was found both in vitro and in mouse brain after infection with a ts mutant of MHV strain A59 and wild type JHM-virus 18''19 Phylogenetic trees constructed from five different windows of the genomes of eight IBV strains were used to detect crossover events. Cloning and sequencing of genes encoding structural proteins of avian infectious bronchitis virus

title:
  Sequence evidence for RNA recombination in field isolates of avian coronavirus infectious bronchitis virus

abstract:
  Abstract Under laboratory conditions coronaviruses were shown to have a high frequency of recombination. In The Netherlands, vaccination against infectious bronchitis virus (IBV) is performed with vaccines that contain several life-attenuated virus strains. These highly effective vaccines may create ideal conditions for recombination, and could therefore be dangerous in the long term. This paper addresses the question of the frequency of recombination of avian coronavirus IBV in the field. A method was sought to detect and quantify recombination from sequence data. Nucleotide sequences of eight IBV isolates in a region of the genome suspected to contain recombination, were aligned and compared. Phylogenetic trees were constructed for different sections of this region. Differences in topology between these trees were observed, suggesting that in three out of eight strains in vivo RNA recombinant had occurred.


id: cord-288938-4bheqtk5
author: Hönemann, M.
date: 2019-10-08
txt: ./txt/cord-288938-4bheqtk5.txt
cache: ./cache/cord-288938-4bheqtk5.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1016/j.vaccine.2019.08.027
doi: 10.1016/j.vaccine.2019.08.027
summary:
  authors: Hönemann, M.; Martin, D.; Pietsch, C.; Maier, M.; Bergs, S.; Bieck, E.; Liebert, U.G. title: Influenza B virus infections in Western Saxony, Germany in three consecutive seasons between 2015 and 2018: Analysis of molecular and clinical features AIM: The aim of the study was to compare laboratory confirmed influenza B cases during three consecutive years with respect to vaccination history, clinical symptoms and molecular virology. c o m / l o c a t e / v a c c i n e cross reactivity is observed [14, 15] , vaccine efficiency between the two lineages might be reduced in seasons in which the formulation of the trivalent influenza vaccine does not match the circulating strain due to antigenic differences [16, 17] . Sequence analysis of the whole hemagglutinin gene was performed for 16 Victoria and 76 Yamagata strains and consistently confirmed the results of the initial lineage determination.

title:
  Influenza B virus infections in Western Saxony, Germany in three consecutive seasons between 2015 and 2018: Analysis of molecular and clinical features

abstract:
  BACKGROUND: The impact of annual influenza epidemics and prevailing strains varies worldwide and regional. The majority of vaccines used contained two influenza A strains and only one influenza B strain (trivalent vaccine). AIM: The aim of the study was to compare laboratory confirmed influenza B cases during three consecutive years with respect to vaccination history, clinical symptoms and molecular virology. METHODS: Partial HA gene sequences were analyzed for lineage determination and complete HA sequence in cases with reported vaccination and in fatal cases. Clinical data were retrieved from patient charts. FINDINGS: During the 2015/16 season, 75 influenza B cases were retrieved; 11 in 2016/17, and 274 in 2017/18. The frequency of Yamagata-lineage strains increased from 7.6% to 100%. No difference was detected in the relative frequency of co-morbidities in season 2017/18. 37.7% of the adult patients and 4.5% of pediatric patients were vaccinated against influenza. INTERPRETATION: Phylogenetically, Yamagata strains clustered similarly in 2017/2018 when compared to the previous two influenza seasons. While the relative frequency of influenza B cases differed, the clinical symptoms remained similar. CONCLUSION: World Health Organization recommendations for the use of tetravalent vaccines that contain two influenza B strains (Yamagata and Victoria) in addition to the two influenza A strains (H1N1 and H3N2) should be implemented in national vaccination guidelines. FUNDING: This research was partially supported by the Association of Sponsors and Friends of Leipzig University.


id: cord-289090-7x2752j4
title: Microbiology of otitis media: A moving target
author: Vergison, Anne
date: 2008-12-23
txt: ./txt/cord-289090-7x2752j4.txt
cache: ./cache/cord-289090-7x2752j4.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1016/j.vaccine.2008.11.006
doi: 10.1016/j.vaccine.2008.11.006
summary:
  Streptococcus pneumoniae, non-encapsulated Haemophilus influenzae, Moraxella catarrhalis, and group A Streptococcus are the leading causes of bacterial AOM worldwide. This review provides some insight into the microbiology of AOM in an era of antibiotic resistance and pneumococcal conjugate vaccine use. Acute otitis media-diagnosis and treatment in the era of antibiotic resistant organisms: updated clinical practice guidelines Can acute otitis media caused by Haemophilus influenzae be distinguished from that caused by Streptococcus pneumoniae? Pneumococcal capsular polysaccharides conjugated to protein D for prevention of acute otitis media caused by both Streptococcus pneumoniae and non-typable Haemophilus influenzae: a randomised double-blind efficacy study Association of clinical signs and symptoms with pneumococcal acute otitis media by serotype -implications for vaccine effect Acute otitis media due to penicillin-nonsusceptible Streptococcus pneumoniae before and after the introduction of the pneumococcal conjugate vaccine

abstract:
  Abstract The microbiology of acute otitis media (AOM) is linked to the nasopharyngeal commensal flora. This respiratory ecosystem undergoes various selective pressures, such as antibiotic consumption and vaccine use. Socio-economic conditions also influence the bacterial composition of the nasopharynx. Streptococcus pneumoniae, non-encapsulated Haemophilus influenzae, Moraxella catarrhalis, and group A Streptococcus are the leading causes of bacterial AOM worldwide. This paper will discuss the causes and consequences of recent shifts in the underlying microbiology of AOM.


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-291510-jh2fdks4
author: Jiang, Yi
date: 2020-02-11
txt: ./txt/cord-291510-jh2fdks4.txt
cache: ./cache/cord-291510-jh2fdks4.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1016/j.vaccine.2020.01.001
doi: 10.1016/j.vaccine.2020.01.001
summary:
  Collectively, our results suggest that the recombinant strain, rH120-S1/YZ, may represent a promising vaccine candidate against QX-like IBVs. Infectious bronchitis (IB) was first described as a respiratory disease affecting chicks in the US in 1931 as an acute and highly contagious viral disease, and continues to cause major economic loss within the poultry industry worldwide [1] [2] [3] . Commercial attenuated live vaccines used against IBV in China include the H120, LDT3, and 4/91 strains [7] ; however, phylogenetic analysis indicates that the QX-like genotype is genetically distant from the strains described above, which may explain the poor cross-protectivity against infection in chickens immunized with these classical vaccines [18, 19] . The earliest death was observed at 3 dpi in the QX-like strain rIBYZ group, which virus was highly pathogenic to one-day-old SPF chickens; the final mortality of this group was 63.3% (Fig. 3A) . Preparation and protective efficacy of a chicken embryo kidney cell-attenuation GI-19/QX-like avian infectious bronchitis virus vaccine

title:
  Recombinant infectious bronchitis coronavirus H120 with the spike protein S1 gene of the nephropathogenic IBYZ strain remains attenuated but induces protective immunity

abstract:
  Infectious bronchitis (IB) is a highly infectious viral disease responsible for major economic losses in the poultry industry. A reverse genetic vaccine is a safe, rapid, and effective method of achieving IB prevention and control. In this study, we constructed the recombinant strain, rH120-S1/YZ, using a reverse genetic system, based on the backbone of the H120 vaccine strain, with the S1 gene replaced with that of the QX-like nephropathogenic strain, ck/CH/IBYZ/2011, isolated in China. The results of dwarf chicken embryos, growth kinetics, and viral titration in the embryos demonstrated that the biological characteristics of the recombinant virus remained unchanged. Like the rH120-infected group and in contrast to the rIBYZ-infected group, no mortality, clinical signs, or lesions were observed in the lungs or kidneys of young chickens inoculated with rH120-S1/YZ. The viral loads in various tissues, cloacal, and oral swabs was lower in most types of samples, indicating that the rH120-S1/YZ strain was highly safe in chicks. Compared to rH120 vaccination group, when the efficacy of this strain was evaluated against the QX-like IBV strain, better protection, with 100% survival rate and no disease symptom or gross lesion was observed in the chickens vaccinated with rH120-S1/YZ. Increased levels of IBV-specific antibodies were detected in the serum of the rH120-S1/YZ-vaccinated animals 14 days post-vaccination. Collectively, our results suggest that the recombinant strain, rH120-S1/YZ, may represent a promising vaccine candidate against QX-like IBVs.


id: cord-292528-8kdhf123
author: Lau, Yuk-Fai
date: 2009-02-25
txt: ./txt/cord-292528-8kdhf123.txt
cache: ./cache/cord-292528-8kdhf123.txt
extension: .txt
mime: text/plain
url: https://www.sciencedirect.com/science/article/pii/S0264410X08017751
doi: 10.1016/j.vaccine.2008.12.048
summary:
  In addition, a number of studies have shown that the hemagglutinin (HA) molecules of avian H5 viruses are poorly immunogenic [1, 2] , where up to 90 g of antigen (6 times the normal dose of human influenza virus HA) was required to elicit potentially protective responses in a substantial number of subjects [2] . Intranasal administration of PIKA produced the most significant anti-influenza effect compared to s.c. or i.p. administration of the drug (Fig. 1D ) though the pul-monary viral titers in the treated mice were still significantly lower than the titers of the PBS control group (p = 0.0079). In summary, we have demonstrated that the inclusion of PIKA in two different formations of influenza vaccine can achieve substantial antigen-sparing with robust humoral immune responses, leading to potent pulmonary viral titer reduction in vivo.

title:
  A TLR3 ligand that exhibits potent inhibition of influenza virus replication and has strong adjuvant activity has the potential for dual applications in an influenza pandemic

abstract:
  The appearance and spread of the H5N1 highly pathogenic avian influenza (HPAI) raise concern of a possible pandemic. Current preventive measures include the development of a pre-pandemic influenza vaccine and stockpiling of neuraminidase inhibitors. However, their benefits can be significantly reduced by mutations in the hemagglutinin or neuraminidase resulting in antigenic changes and the appearance of drug-resistance, respectively. Drugs that target the innate immune system to achieve a ‘heightened antiviral’ state represent another class of antiviral agents that could contribute to the control and treatment of influenza infection. In this study, PIKA (a stabilized dsRNA) provides broad-spectrum prophylaxis against a number of influenza A viruses. In addition, when PIKA was admixed with influenza vaccine preparations, including a formalin-inactivated whole-virion H5 vaccine, significant adjuvanting effect leading to accelerated viral clearance was observed in a murine model. These biological effects appear to be mediated by the ability of PIKA to promote the maturation of dendritic cells, including up-regulation of co-stimulatory molecules, such as CD80 and CD86, and the induction of various cytokines and chemokines. Toll-like receptor 3 (TLR3) was shown to recognize PIKA in a concentration-dependent manner. The potency and versatility in its activities make PIKA an attractive candidate for use in an influenza pandemic.


id: cord-293234-ouykx6g5
author: Puig-Barberà, J.
date: 2012-08-24
txt: ./txt/cord-293234-ouykx6g5.txt
cache: ./cache/cord-293234-ouykx6g5.txt
extension: .txt
mime: text/plain
url: https://api.elsevier.com/content/article/pii/S0264410X12010079
doi: 10.1016/j.vaccine.2012.07.006
summary:
  title: Effectiveness of the 2010–2011 seasonal influenza vaccine in preventing confirmed influenza hospitalizations in adults: A case–case comparison, case-control study INTRODUCTION: We estimated influenza vaccine effectiveness (IVE) to prevent laboratory-confirmed influenza-related hospitalizations in patients 18 years old or older during the 2010–2011 influenza season. Using a prospective case-case comparison approach, we have estimated seasonal influenza vaccine effectiveness (IVE) to prevent laboratory confirmed influenza-related hospitalizations in adults. When restricting the comparison, between cases and controls, by the presence of high-risk conditions, the differences that remained significant were age, 23-valent pneumococcal vaccination, and having been vaccinated with the previous or current season influenza vaccines (Table 2) . When restricted to those 60 years old or older, age and influenza vaccination with the previous or current seasonal influenza vaccine remained as significant differences between cases and controls ( Table 2 ).

title:
  Effectiveness of the 2010–2011 seasonal influenza vaccine in preventing confirmed influenza hospitalizations in adults: A case–case comparison, case-control study

abstract:
  INTRODUCTION: We estimated influenza vaccine effectiveness (IVE) to prevent laboratory-confirmed influenza-related hospitalizations in patients 18 years old or older during the 2010–2011 influenza season. METHODS: We conducted a prospective case-control study in five hospitals, in Valencia, Spain. Study subjects were consecutive emergency hospitalizations for predefined conditions associated with an influenza-like illness episode <8 days before admission. Patients were considered immunized if vaccinated ≥14 days before influenza-like illness onset. Cases were those with a real time reverse transcriptase polymerase chain reaction (RT-PCR) positive for influenza and controls were RT-PCR positive for other respiratory viruses. Adjusted IVE was estimated as 100 × (1 − adjusted odds ratio). To account for indication bias we computed adjusted IVE for respiratory syncytial virus related hospitalizations. RESULTS: Of 826 eligible hospitalized patients, 102 (12%) were influenza positive and considered cases, and 116 (14%) were positive for other respiratory viruses and considered controls. Adjusted IVE was 54% (95% confidence interval, 11–76%). By subgroup, adjusted IVE was 53% (4–77%) for those with high-risk conditions, 59% (16–79%) for those ≥60 years of age, and, 54% (4–79%) for those ≥60 years of age with high-risk conditions. No influenza vaccine effect was observed against respiratory syncytial virus related hospitalization. CONCLUSION: Influenza vaccination was associated with a significant reduction on the risk of confirmed influenza hospitalization, irrespective of age and high-risk conditions.


id: cord-293360-nmttgxlq
title: Acceptance of a COVID-19 vaccine: A multifactorial consideration
author: García, Leidy Y.
date: 2020-11-10
txt: ./txt/cord-293360-nmttgxlq.txt
cache: ./cache/cord-293360-nmttgxlq.txt
extension: .txt
mime: text/plain
url: https://www.sciencedirect.com/science/article/pii/S0264410X20313207
doi: 10.1016/j.vaccine.2020.10.026
abstract: nan
summary:
  Specifically, the willingness to vaccinate against SARS-CoV-2 depends on: (a) Availability, i.e. the actual existence of an effective vaccine and its country of origin; (b) Access to the vaccine, which could be limited by individual or governmental budgetary restrictions to finance preventive public health measures; (c) Perceived health risk, which depends on the intensity and severity of side effects and COVID-19 prevalence; (d) Information on benefits, risks and access pathways; (e) Previous experience with other vaccines and exposure to diseases, as this affects risk perception; and (f) Sociodemographic factors including age, education level, gender and more. [4] and Harrison [5] , a transparent educational and communicative campaign is needed, one that considers interaction between health policymakers in a way that allows people to value the personal and social benefit of being vaccinated against COVID-19, reducing hesitation.


id: cord-294302-hboc3xcz
title: COVID-19 vaccine and boosted immunity: nothing ad interim to do?
author: Roncati, Luca
date: 2020-10-09
url: https://doi.org/10.1016/j.vaccine.2020.10.013
doi: 10.1016/j.vaccine.2020.10.013
abstract:
  SUMMARY Today, Coronavirus Disease 2019 (COVID-19) is a global public health emergency and vaccination measures to counter its diffusion are deemed necessary. Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the etiological agent of the disease, unleashes a T-helper 2 immune response in those patients requiring intensive care. Here, we illustrate the immunological mechanism to train the immune system towards a more effective and less symptomatic T-helper 1 (Th1) immune response, thanks to a subcutaneous vaccine containing lysates of Corynebacterium parvum (synonym for Propionibacterium acnes), a Gram-positive bacterium able to evoke a strong Th1 response.


id: cord-294789-07hto8qn
author: Schoch-Spana, Monica
date: 2020-10-29
url: https://api.elsevier.com/content/article/pii/S0264410X20313682
doi: 10.1016/j.vaccine.2020.10.059
title:
  The public’s role in COVID-19 vaccination: human-centered recommendations to enhance pandemic vaccine awareness, access, and acceptance in the United States

abstract:
  Given the social and economic upheavals caused by the COVID-19 pandemic, political leaders, health officials, and members of the public are eager for solutions. One of the most promising, if they can be successfully developed, is vaccines. While the technological development of such countermeasures is currently underway, a key social gap remains. Past experience in routine and crisis contexts demonstrates that uptake of vaccines is more complicated than simply making the technology available. Vaccine uptake, and especially the widespread acceptance of vaccines, is a social endeavor that requires consideration of human factors. To provide a starting place for this critical component of a future COVID-19 vaccination campaign in the United States, the 23-person Working Group on Readying Populations for COVID-19 Vaccines was formed. One outcome of this group is a synthesis of the major challenges and opportunities associated with a future COVID-19 vaccination campaign and empirically-informed recommendations to advance public understanding of, access to, and acceptance of vaccines that protect against SARS-CoV-2. While not inclusive of all possible steps than could or should be done to facilitate COVID-19 vaccination, the working group believes that the recommendations provided are essential for a successful vaccination program.


id: cord-294856-eeh2a0t8
author: Lambert, Paul-Henri
date: 2020-05-25
txt: ./txt/cord-294856-eeh2a0t8.txt
cache: ./cache/cord-294856-eeh2a0t8.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/32507409/
doi: 10.1016/j.vaccine.2020.05.064
summary:
  Therefore, CEPI and the Brighton Collaboration Safety Platform for Emergency vACcines (SPEAC) convened a scientific working meeting https://brightoncollaboration.us/brighton-collaboration-cepi-covid-19-web-conference/) on March 12 and 13, 2020 of experts in the field of vaccine immunology and coronaviruses to discuss current knowledge that could form the basis for the assessment of the risk of enhanced disease during SARS-CoV-2 vaccine development. Ferret models of SARS-CoV-1 also demonstrate virus replication in respiratory tracts with induction of a neutralizing antibody response but also demonstrated little evidence of clinical disease [13] . Efficacy of several SARS-CoV-1 vaccines was evaluated in these models with spike (S) protein based vaccines demonstrating neutralizing antibody and protection against pulmonary replication of the challenge virus in mice and hamsters [16] . There is evidence for disease enhancement in vaccinated animals after challenge with live virus in multiple studies with SARS-CoV-1 vaccine candidates as summarized in Table. Chinese macaques immunized with a modified vaccinia virus expressing S protein then challenged with SARS-CoV-1 did not develop clinical disease, but histopathology showed lung injury.

title:
  Consensus Summary Report for CEPI/BC March 12-13, 2020 Meeting: Assessment of Risk of Disease Enhancement with COVID-19 Vaccines

abstract:
  A novel coronavirus (CoV), Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), emerged in late 2019 in Wuhan, China and has since spread as a global pandemic. Safe and effective vaccines are thus urgently needed to reduce the significant morbidity and mortality of Coronavirus Disease 2019 (COVID-19) disease and ease the major economic impact. There has been an unprecedented rapid response by vaccine developers with now over one hundred vaccine candidates in development and at least six having reached clinical trials. However, a major challenge during rapid development is to avoid safety issues both by thoughtful vaccine design and by thorough evaluation in a timely manner. A syndrome of “disease enhancement” has been reported in the past for a few viral vaccines where those immunized suffered increased severity or death when they later encountered the virus or were found to have an increased frequency of infection. Animal models allowed scientists to determine the underlying mechanism for the former in the case of Respiratory Syncytial virus (RSV) vaccine and have been utilized to design and screen new RSV vaccine candidates. Because some Middle East respiratory syndrome (MERS) and SARS-CoV-1 vaccines have shown evidence of disease enhancement in some animal models, this is a particular concern for SARS-CoV-2 vaccines. To address this challenge, the Coalition for Epidemic Preparedness Innovations (CEPI) and the Brighton Collaboration (BC) Safety Platform for Emergency vACcines (SPEAC) convened a scientific working meeting on March 12 and 13, 2020 of experts in the field of vaccine immunology and coronaviruses to consider what vaccine designs could reduce safety concerns and how animal models and immunological assessments in early clinical trials can help to assess the risk. This report summarizes the evidence presented and provides considerations for safety assessment of COVID-19 vaccine candidates in accelerated vaccine development.


id: cord-295191-xu26mvc3
title: Complement and its role in protection and pathogenesis of flavivirus infections
author: Avirutnan, Panisadee
date: 2008-12-30
url: https://www.sciencedirect.com/science/article/pii/S0264410X08016083
doi: 10.1016/j.vaccine.2008.11.061
abstract:
  The complement system is a family of serum and cell surface proteins that recognize pathogen-associated molecular patterns, altered-self ligands, and immune complexes. Activation of the complement cascade triggers several antiviral functions including pathogen opsonization and/or lysis, and priming of adaptive immune responses. In this review, we will examine the role of complement activation in protection and/or pathogenesis against infection by Flaviviruses, with an emphasis on experiments with West Nile and Dengue viruses.


id: cord-295850-nb6miso7
author: Zhang, Chuan-hai
date: 2005-05-02
txt: ./txt/cord-295850-nb6miso7.txt
cache: ./cache/cord-295850-nb6miso7.txt
extension: .txt
mime: text/plain
url: https://www.sciencedirect.com/science/article/pii/S0264410X05000939
doi: 10.1016/j.vaccine.2004.11.073
summary:
  title: Immune responses in Balb/c mice induced by a candidate SARS-CoV inactivated vaccine prepared from F69 strain The immunogenicity of a candidate-inactivated vaccine prepared from SARS-CoV F69 strain was evaluated in Balb/c mice. The present study was performed with the objective of determining the immunogenicity of a candidate-inactivated SARS-CoV vaccine made from F69 strain in Balb/c mice. In test groups, anti-SARS-CoV specific IgM antibodies were induced by the inactivated vaccine. The results showed that SARS-CoV F69 strain inactivated vaccine could induce potent humoral immune responses in Balb/c mice. In present study, the specificity of serum antibodies induced by F69 strain inactivated vaccine was identified by Western blot assay. A convalescent serum of SARS patient was used, and the same positive result was obtained (lane 3, Fig. 4) , which further demonstrated the specificity of the antibodies induced with the inactivated vaccine produced from F69 strain.

title:
  Immune responses in Balb/c mice induced by a candidate SARS-CoV inactivated vaccine prepared from F69 strain

abstract:
  The immunogenicity of a candidate-inactivated vaccine prepared from SARS-CoV F69 strain was evaluated in Balb/c mice. Potent humoral immune responses were induced under the elicitation of three times of immunizations at 2-week intervals with this vaccine, combined with three types of adjuvants (Freund's adjuvant, Al(OH)(3) adjuvant and CpG adjuvant). Titers of specific IgG antibodies in three test groups all peaked in the sixth week after first vaccination, but significant differences existed in the kinetics of specific IgG antibody levels. The strong neutralizing capacity exhibited in micro-cytopathic effect neutralization tests indicated the specific antibodies are protective. Western blot assay further demonstrated the specificity of the induced serum antibodies.


id: cord-296469-h0ma163u
title: Preparing for the unpredictable: The continuing need for pandemic influenza preparedness
author: Gellin, Bruce G.
date: 2016-10-26
txt: ./txt/cord-296469-h0ma163u.txt
cache: ./cache/cord-296469-h0ma163u.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/27682508/
doi: 10.1016/j.vaccine.2016.09.023
abstract: nan
summary:
  Of the many things that need to be in place to prepare for and respond to the next influenza pandemic, vaccines -together with the capacity to mount a timely global vaccination effort -are paramount. But as we learned in the 2009 influenza pandemic, although our response time has improved, a significant shift in approach is needed if an effective vaccine is to be in place before the next pandemic emerges. Until such a universal influenza vaccine becomes available, global influenza vaccine production capacity needs to be ready to respond when the next pandemic emerges. Without a concomitant increase in global demand for seasonal influenza vaccine, the capacity that will produce the world''s pandemic vaccines that GAP has stimulated cannot be sustained [18] .


id: cord-297022-zs5m36cp
title: Appropriate measures of influenza immunization program effectiveness
author: Kwong, Jeffrey C.
date: 2007-01-22
txt: ./txt/cord-297022-zs5m36cp.txt
cache: ./cache/cord-297022-zs5m36cp.txt
extension: .txt
mime: text/plain
url: https://api.elsevier.com/content/article/pii/S0264410X06010759
doi: 10.1016/j.vaccine.2006.09.080
summary:
  Groll and Thomson''s evaluation of the effectiveness of Ontario''s Universal Influenza Immunization Campaign used per capita cases of laboratory-confirmed influenza. A better measure of viral activity is the proportion of influenza tests positive; whereas the weekly proportion of tests positive was relatively consistent, a marked increase over time in the numbers of laboratory-confirmed cases paralleled an increase in the number of tests performed. Regardless, for evaluating universal influenza immunization program effectiveness, other established and available measures employed in previous studies describing the epidemiology of influenza should be used instead of laboratory data. In their evaluation of Ontario''s Universal Influenza Immunization Campaign, Groll and Thomson state that there is a lack of high-quality influenza outcome data in Ontario, so instead they examined the effectiveness of the program using per capita cases of laboratory-confirmed influenza [1] . A better measure of viral activity is the proportion of influenza tests positive (the number of cases of lab-confirmed influenza divided by the number of tests performed).

abstract:
  Groll and Thomson's evaluation of the effectiveness of Ontario's Universal Influenza Immunization Campaign used per capita cases of laboratory-confirmed influenza. We argue that these data are susceptible to various biases and should not be used as an outcome measure. Laboratory data are traditionally used to identify the presence of influenza activity rather than to identify levels of influenza activity. A better measure of viral activity is the proportion of influenza tests positive; whereas the weekly proportion of tests positive was relatively consistent, a marked increase over time in the numbers of laboratory-confirmed cases paralleled an increase in the number of tests performed. Regardless, for evaluating universal influenza immunization program effectiveness, other established and available measures employed in previous studies describing the epidemiology of influenza should be used instead of laboratory data.


id: cord-298551-ua90xoak
title: Influenza epidemiology among hospitalized children in Stockholm, Sweden 1998–2014
author: Bennet, Rutger
date: 2016-06-14
txt: ./txt/cord-298551-ua90xoak.txt
cache: ./cache/cord-298551-ua90xoak.txt
extension: .txt
mime: text/plain
url: https://www.sciencedirect.com/science/article/pii/S0264410X16302560
doi: 10.1016/j.vaccine.2016.04.082
summary:
  The hospital is a tertiary referral center with surgery and a pediatric intensive care unit (PICU) with resources for extracorporeal membrane oxygenation (ECMO), but only children resident in the catchment area were included in the study. The yearly incidence rates in different age groups varied considerably, with median (range) for children <5 years 59 (19Previously known risk factors were found in 312/922 (34% , Table 1 ), the most important being neuromuscular disease (131 cases) and chronic lung disease (40 cases). This is a report of children hospitalized for influenza A or B in a defined population in the northern Stockholm area 1998-2014, covering the pre-pandemic period, including the 2003-2004 outbreak, the 2009 pandemic, and four post-pandemic seasons. In contrast to the known effect of trivalent influenza vaccine (the only one used during the studied period except for the pandemic year) in healthy children >18 months, less is known about its effect in younger children and in those with risk factors.

abstract:
  BACKGROUND: Influenza remains a common reason for the hospitalization of children. There is a need for long term studies that are also population based. We describe the epidemiology of severe influenza in a defined population 1998–2014. METHOD: Retrospective study of annually collected data of virologically confirmed influenza in hospitalized children 0–17 years living in the catchment area (230,000 children). We gathered information about comorbidity and complications from case records, and compared Influenza A, B and A(H1N1)pdm09 with respect to these factors. RESULTS: A total of 922 children with influenza were hospitalized. The mean rate remained unchanged at 22.5–24.2 per 100,000 children per year. There were two major outbreaks: influenza A(H3N2) in 2003–2004 and the A(H1N1) pandemic in 2009–2010. The proportion of children with influenza B increased from 8% during the first half of the study period to 28% during the second half. The highest admission rate was found in children <3 months of age, 169 per 100,000. Children with influenza B were older than those with influenza A. Comorbidity was found in 34%, complications in 41%, and 11% needed intensive care management. The mortality rate was 0.17/100,000 children. CONCLUSION: Influenza remains an important reason for the hospitalization of children, especially during the first years of life. The increasing proportion of influenza B may have to be considered when recommending influenza vaccines.


id: cord-299323-riotkgj4
author: Seo, Yurim
date: 2020-10-13
txt: ./txt/cord-299323-riotkgj4.txt
cache: ./cache/cord-299323-riotkgj4.txt
extension: .txt
mime: text/plain
url: https://api.elsevier.com/content/article/pii/S0264410X20312494
doi: 10.1016/j.vaccine.2020.09.067
summary:
  The key documents examined were the U.S. Food & Drug Administration''s (FDA) Package Inserts (PIs), U.S. Centers for Disease Control and Prevention''s (CDC) Vaccine Information Statements (VISs), and the European Medicines Agency''s (EMA) Summary of Product Characteristics (SmPCs) and Package Leaflets (PLs). Although efforts by the International Council for Harmonization (ICH) to harmonize technical requirements for registering drugs and biologics have produced a number of useful guidelines that are used around the world, such efforts have not been extended to the regulatory review process or product labeling [1] . This study compared vaccine prescribing information and patient information leaflet languages between FDA/Centers for Disease Control and Prevention (CDC) and EMA. The centralized route allows companies to submit a single Marketing Authorization Application (MAA) to EMA that leads to the product''s approval in all countries within the European Economic Area (i.e., the 27 member states of the EU plus Iceland, Liechtenstein and Norway).

title:
  Elements of Regulatory Dissonance: Examining FDA and EMA Product Labeling of New Vaccines (2006–2018)

abstract:
  With the ongoing globalization of the pharmaceutical industry, efforts to harmonize technical requirements of registering drugs and biologics, including vaccines, have produced a number of useful guidelines utilized around the world. However, such efforts have not been extended to the regulatory review process or product labeling. Prescribing information and patient information leaflet are two types of such product labeling documents. This study examined the differences in the languages of these documents between the United States (US) and European Union (EU). The key documents examined were the U.S. Food & Drug Administration’s (FDA) Package Inserts (PIs), U.S. Centers for Disease Control and Prevention’s (CDC) Vaccine Information Statements (VISs), and the European Medicines Agency’s (EMA) Summary of Product Characteristics (SmPCs) and Package Leaflets (PLs). Prescribing information and patient information leaflet languages were subsequently organized into ten and seven categories, respectively. Comparison of FDA PIs to EMA SmPCs showed little harmonization between the two regions, and CDC VISs to EMA PLs revealed even less.


id: cord-299952-xvtt8fz8
author: Gao, LuLu
date: 2010-06-17
txt: ./txt/cord-299952-xvtt8fz8.txt
cache: ./cache/cord-299952-xvtt8fz8.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1016/j.vaccine.2010.03.062
doi: 10.1016/j.vaccine.2010.03.062
summary:
  title: A randomized controlled trial of low-dose recombinant human interferons α-2b nasal spray to prevent acute viral respiratory infections in military recruits To assess the efficacy and safety of a low-dose recombinant human interferon α-2b (rIFNα-2b) nasal spray in preventing acute viral respiratory infections in military population, we performed this randomized controlled trial. To evaluate the efficacy and safety of this new nasal spray in preventing acute respiratory infections in military population, we performed this randomized, placebo-controlled, double-blind trial. In summary, this randomized controlled trial suggested that the recombinant human interferon ␣-2b nasal spray can be used to prevent common acute viral respiratory infections caused by Flu-A, Flu-B, PIV1-3 and ADV and was generally well tolerated among military recruits. The efficacy of preventing viral respiratory infections by the rIFN␣-2b nasal spray should be evaluated further in different population groups, such as children and the elderly, and more samples should be involved in the further study.

title:
  A randomized controlled trial of low-dose recombinant human interferons α-2b nasal spray to prevent acute viral respiratory infections in military recruits

abstract:
  The military population has a high disease burden of acute viral respiratory infections in China. To assess the efficacy and safety of a low-dose recombinant human interferon α-2b (rIFNα-2b) nasal spray in preventing acute viral respiratory infections in military population, we performed this randomized controlled trial. The results showed that application of the rIFNα-2b nasal spray had the benefits in prevention of infections caused by influenza A virus, influenza B virus parainfluenza viruses 1–3 and adenovirus species B. However, no benefit was seen in preventing respiratory syncytial virus. No severe adverse events were reported. Therefore, the rIFNα-2b nasal spray was effective and well tolerated for preventing common viral respiratory infections in the military recruits.


id: cord-301601-4vkag60z
title: Recombinant measles AIK-C vaccine strain expressing heterologous virus antigens
author: Nakayama, Tetsuo
date: 2016-01-04
txt: ./txt/cord-301601-4vkag60z.txt
cache: ./cache/cord-301601-4vkag60z.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1016/j.vaccine.2015.10.127
doi: 10.1016/j.vaccine.2015.10.127
summary:
  Recombinant measles vaccine candidates have been developed and express several heterologous virus protective antigens. The recent development of measles vaccine-based vectored vaccine candidates has been reviewed and some information on recombinant measles vaccines expressing respiratory syncytial virus proteins has been shown and discussed. The live attenuated measles vaccine has been investigated for the recombinant virus vector besides the yellow fever vaccine. When considering a clinical usage of recombinant measles vaccine candidates expressing RSV antigen in young infants, growth inhibition of vaccine virus was supposed because of maternally conferred immunity. Recombinant measles viruses expressing single or multiple antigens of human immunodeficiency virus (HIV-1) induce cellular and humoral immune responses Broadly neutralizing immune responses against hepatitis C virus induced by vectored measles viruses and a recombinant envelope protein booster AIK-C measles vaccine expressing fusion protein of respiratory syncytial virus induces protective antibodies in cotton rats Recombinant measles viruses expressing respiratory syncytial virus proteins induced virus-specific CTL responses in cotton rats

abstract:
  Further attenuated measles vaccines were developed more than 50 years ago and have been used throughout the world. Recombinant measles vaccine candidates have been developed and express several heterologous virus protective antigens. Immunogenicity and protective actions were confirmed using experimental animals: transgenic mice, cotton rats, and primates. The recent development of measles vaccine-based vectored vaccine candidates has been reviewed and some information on recombinant measles vaccines expressing respiratory syncytial virus proteins has been shown and discussed.


id: cord-302222-9ad0fw6z
title: Vaccines against diseases transmitted from animals to humans: A one health paradigm
author: Monath, Thomas P.
date: 2013-11-04
txt: ./txt/cord-302222-9ad0fw6z.txt
cache: ./cache/cord-302222-9ad0fw6z.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1016/j.vaccine.2013.09.029
doi: 10.1016/j.vaccine.2013.09.029
summary:
  A number of examples of the use of Framework II vaccines are provided, e.g. against brucellosis, Escherischia coli O157, rabies, Rift Valley fever, Venezuelan equine encephalitis, and Hendra virus. Overall, it remains to be seen which of the many Rift Valley fever vaccines in development progress to regulatory approval and whether an integrated veterinary and human health policy based on the immunization of livestock in Africa together with predictive surveillance, can abort impending outbreaks, and lead to long range control of this important disease. The increasing problem of emerging infections, the majority of which are the result of spill-over from animals to humans, is a compelling reason to consider novel vaccine interventions, and the collaborations between veterinary and human health institutions in the development of the Hendra, West Nile, VEE and Rift Valley fever vaccines described in this review serve as examples of the power of this approach.

abstract:
  Abstract This review focuses on the immunization of animals as a means of preventing human diseases (zoonoses). Three frameworks for the use of vaccines in this context are described, and examples are provided of successes and failures. Framework I vaccines are used for protection of humans and economically valuable animals, where neither plays a role in the transmission cycle. The benefit of collaborations between animal health and human health industries and regulators in developing such products is discussed, and one example (West Nile vaccine) of a single product developed for use in animals and humans is described. Framework II vaccines are indicated for domesticated animals as a means of preventing disease in both animals and humans. The agents of concern are transmitted directly or indirectly (e.g. via arthropod vectors) from animals to humans. A number of examples of the use of Framework II vaccines are provided, e.g. against brucellosis, Escherischia coli O157, rabies, Rift Valley fever, Venezuelan equine encephalitis, and Hendra virus. Framework III vaccines are used to immunize wild animals as a means of preventing transmission of disease agents to humans and domesticated animals. Examples are reservoir-targeted, oral bait rabies, Mycobacterium bovis and Lyme disease vaccines. Given the speed and lost cost of veterinary vaccine development, some interventions based on the immunization of animals could lead to rapid and relatively inexpensive advances in public health. Opportunities for vaccine-based approaches to preventing zoonotic and emerging diseases that integrate veterinary and human medicine (the One Health paradigm) are emphasized.


id: cord-302265-97sxlkjp
title: Immunogenicity of a malaria parasite antigen displayed by Lactococcus lactis in oral immunisations
author: Ramasamy, R.
date: 2006-05-01
txt: ./txt/cord-302265-97sxlkjp.txt
cache: ./cache/cord-302265-97sxlkjp.txt
extension: .txt
mime: text/plain
url: https://api.elsevier.com/content/article/pii/S0264410X06002106
doi: 10.1016/j.vaccine.2006.02.040
summary:
  A putative protective protein from Plasmodium falciparum merozoites, MSA2, was expressed in two different ways on the cell surface of the Gram-positive food-grade bacterium, Lactococcus lactis. In a second display format, MSA2 was fused to the peptidoglycan-binding domain (Protein Anchor) of the lactococcal cell wall hydrolase AcmA and was non-covalently rebound to the surface of non-genetically modified, non-living high-binder L. lactis recombinants carrying covalently bound MSA2 were used to immunise rabbits through nasal and oral routes. lactis-pNG3043 for immunisation were prepared from overnight cultures (the latter strain was induced overnight with nisin A for MSA2-Cov expression) and stored in aliquots of 10 11 colony forming units (cfu) per ml growth medium containing 10% glycerol at −80 • C. lactis-pNG3041(MSA2-Cov) or 5 × 10 10 GEM particles with bound MSA2-nCov. Each dose was repeated for three successive days to obtain reproducible oral immunisation. lactis response was even more minimized in the rabbit orally immunised with the GEM particle vaccine (Fig. 5C ).

abstract:
  A putative protective protein from Plasmodium falciparum merozoites, MSA2, was expressed in two different ways on the cell surface of the Gram-positive food-grade bacterium, Lactococcus lactis. The first display format exploits an LPXTG-type anchoring motif of the lactococcal proteinase PrtP to covalently anchor MSA2 to the genetically modified producer cells. In a second display format, MSA2 was fused to the peptidoglycan-binding domain (Protein Anchor) of the lactococcal cell wall hydrolase AcmA and was non-covalently rebound to the surface of non-genetically modified, non-living high-binder L. lactis cells, termed Gram-positive enhancer matrix (GEM) particles. The L. lactis recombinants carrying covalently bound MSA2 were used to immunise rabbits through nasal and oral routes. The highest levels of IgG antibodies reacting with near-native MSA2 on merozoites was elicited by oral administration. Intestinal antibodies to MSA2 were produced only after oral immunisation. MSA2-specific T(h)-cell activation could be demonstrated. Based on these results, the immunogenicity in oral immunisations of MSA2, bound non-covalently to non-genetically modified L. lactis GEM particles, was compared with MSA2 that was bound covalently to genetically modified L. lactis. These two forms elicited similar titres of serum antibodies. The results illustrate the potential of using non-genetically modified L. lactis as a safe vaccine delivery vehicle to elicit systemic antibodies, thereby avoiding the dissemination of recombinant DNA into the environment.


id: cord-303056-bdse9o26
author: Okada, Masaji
date: 2007-04-20
url: https://www.ncbi.nlm.nih.gov/pubmed/17289225/
doi: 10.1016/j.vaccine.2007.01.032
title:
  Development of vaccines and passive immunotherapy against SARS corona virus using SCID-PBL/hu mouse models

abstract:
  We have investigated novel vaccine strategies against severe acute respiratory syndrome (SARS) CoV using cDNA constructs encoding the structural antigens: (S), (M), (E), or (N) protein, derived from SARS CoV. PBL from healthy human volunteers were administered i.p. into IL-2 receptor γ-chain disrupted SCID mice, and SCID-PBL/hu mice were constructed. These mice can be used to analyze the human immune response in vivo. SARS M DNA vaccine and N DNA vaccine induced human CTL specific for SARS CoV antigens. Alternatively, SARS M DNA vaccines inducing human neutralizing antibodies and human monoclonal antibodies against SARS CoV are now being developed. These results show that these vaccines can induce virus-specific immune responses and should provide a useful tool for development of protective and therapeutic vaccines.


id: cord-303200-hwvkvdlk
author: Decaro, Nicola
date: 2007-01-26
url: https://www.ncbi.nlm.nih.gov/pubmed/17092616/
doi: 10.1016/j.vaccine.2006.10.020
title:
  Occurrence of severe gastroenteritis in pups after canine parvovirus vaccine administration: A clinical and laboratory diagnostic dilemma

abstract:
  Abstract A total of 29 faecal samples collected from dogs with diarrhoea following canine parvovirus (CPV) vaccination were tested by minor groove binder (MGB) probe assays for discrimination between CPV vaccine and field strains and by diagnostic tests for detection of other canine pathogens. Fifteen samples tested positive only for CPV field strains; however, both vaccine and field strains were detected in three samples. Eleven samples were found to contain only the vaccine strain, although eight of them tested positive for other pathogens of dogs. Only three samples were found to contain the vaccine strain without evidence of canine pathogens. The present study confirms that most cases of parvovirus-like disease occurring shortly after vaccination are related to infection with field strains of canine parvovirus type 2 (CPV-2) rather than to reversion to virulence of the modified live virus contained in the vaccine.


id: cord-304807-j2k1oel2
author: Herrera-Rodriguez, José
date: 2019-03-14
url: https://www.sciencedirect.com/science/article/pii/S0264410X19301847
doi: 10.1016/j.vaccine.2019.01.086
title:
  Inactivated or damaged? Comparing the effect of inactivation methods on influenza virions to optimize vaccine production

abstract:
  The vast majority of commercially available inactivated influenza vaccines are produced from egg-grown or cell-grown live influenza virus. The first step in the production process is virus inactivation with β-propiolactone (BPL) or formaldehyde (FA). Recommendations for production of inactivated vaccines merely define the maximal concentration for both reagents, leaving the optimization of the process to the manufacturers. We assessed the effect of inactivation with BPL and FA on 5 different influenza virus strains. The properties of the viral formulation, such as successful inactivation, preservation of hemagglutinin (HA) binding ability, fusion capacity and the potential to stimulate a Toll-like receptor 7 (TLR7) reporter cell line were then assessed and compared to the properties of the untreated virus. Inactivation with BPL resulted in undetectable infectivity levels, while FA-treated virus retained very low infectious titers. Hemagglutination and fusion ability were highly affected by those treatments that conferred higher inactivation, with BPL-treated virus binding and fusing at a lower degree compared to FA-inactivated samples. On the other hand, BPL-inactivated virus induced higher levels of activation of TLR7 than FA-inactivated virus. The alterations caused by BPL or FA treatments were virus strain dependent. This data shows that the inactivation procedures should be tailored on the virus strain, and that many other elements beside the concentration of the inactivating agent, such as incubation time and temperature, buffer and virus concentration, have to be defined to achieve a functional product.


id: cord-307939-rydgncys
title: Willingness to accept a future influenza A(H7N9) vaccine in Beijing, China
author: Wu, Shuangsheng
date: 2018-01-25
txt: ./txt/cord-307939-rydgncys.txt
cache: ./cache/cord-307939-rydgncys.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/29246476/
doi: 10.1016/j.vaccine.2017.12.008
summary:
  The variables that were significantly associated with a higher likelihood of reporting willingness were being younger adults (aged 18–29 years: OR = 1.52, 95% CI: 1.17–1.97; aged 30–39 years: OR = 1.39, 95% CI: 1.08–1.78), being farmers (OR = 1.61; 95% CI: 1.32–1.96), being unemployed people (OR = 1.36; 95% CI: 1.04–1.78), living in suburban areas (OR = 2.18; 95% CI: 1.89–2.51), having ≥2 children in the family (OR = 1.41; 95% CI: 1.03–1.92), perceived risk in China (OR = 1.30; 95% CI: 1.15–1.48), perceived susceptibility to disease (OR = 3.13; 95% CI: 2.73–3.58), perceived negative effect on daily life (OR = 1.32; 95% CI: 1.13–1.55), perceived effectiveness of vaccination (OR = 2.34; 95% CI: 2.07–2.64), and recent uptake of influenza vaccine (OR = 2.26; 95% CI: 1.92–2.66). In the present study, we conducted a large population-based cross-sectional survey to estimate residents'' willingness to accept a future H7N9 vaccine and to identify its associated possible factors in the general adult population of Beijing at the end of the second epidemic wave.

abstract:
  BACKGROUND: The present study aimed to estimate residents’ willingness to accept a future H7N9 vaccine and its determinants in the general adult population in Beijing, China. METHODS: We conducted a multi-stage sampling, cross-sectional survey using self-administered anonymous questionnaires from May to June, in 2014. The main outcome variable was residents’ willingness to accept a future H7N9 vaccine. Logistic regression was used to identify the predictors of vaccination willingness. RESULTS: Of the 7264 eligible participants, 14.5% of Beijing residents reported that they had not heard of H7N9. Among those who had heard of H7N9, 59.5% of the general adult population would be willing to accept a future H7N9 vaccine, and approximately half of them reported ‘I am afraid of being infected by H7N9’ and ‘H7N9 vaccine can prevent infections’, and 28.1% reported ‘my daily life is affected by H7N9’. The variables that were significantly associated with a higher likelihood of reporting willingness were being younger adults (aged 18–29 years: OR = 1.52, 95% CI: 1.17–1.97; aged 30–39 years: OR = 1.39, 95% CI: 1.08–1.78), being farmers (OR = 1.61; 95% CI: 1.32–1.96), being unemployed people (OR = 1.36; 95% CI: 1.04–1.78), living in suburban areas (OR = 2.18; 95% CI: 1.89–2.51), having ≥2 children in the family (OR = 1.41; 95% CI: 1.03–1.92), perceived risk in China (OR = 1.30; 95% CI: 1.15–1.48), perceived susceptibility to disease (OR = 3.13; 95% CI: 2.73–3.58), perceived negative effect on daily life (OR = 1.32; 95% CI: 1.13–1.55), perceived effectiveness of vaccination (OR = 2.34; 95% CI: 2.07–2.64), and recent uptake of influenza vaccine (OR = 2.26; 95% CI: 1.92–2.66). CONCLUSIONS: A great number of Beijing residents had doubts about the vaccine’s effectiveness and were not concerned about disease risk, which were the factors affecting willingness to be vaccinated. Targeted education programs on disease risk as well as vaccine’s effectiveness are needed to improve the willingness of vaccination for potential H7N9 pandemic preparedness.


id: cord-309999-izdl0f2i
title: Immunogenicity and protective efficacy in monkeys of purified inactivated Vero-cell SARS vaccine
author: Qin, Ede
date: 2006-02-13
txt: ./txt/cord-309999-izdl0f2i.txt
cache: ./cache/cord-309999-izdl0f2i.txt
extension: .txt
mime: text/plain
url: https://api.elsevier.com/content/article/pii/S0264410X05008960
doi: 10.1016/j.vaccine.2005.06.038
summary:
  Additionally, three groups of rhesus monkeys were immunized with different doses of the purified inactivated SARS vaccine (0.5, 1 and 2 μg/time/monkey) on days 0 and 7, and the monkeys were challenged with SARS-CoV GZ-01 strain. INTERPRETATION: The purified inactivated SARS vaccine could induce high levels of neutralizing antibody, and protect the monkeys from the challenge of SARS-CoV. The results showed that both the purified and the unpurified SARS vaccines can induce high levels of SARS-CoV specific neutralizing antibodies in monkeys, thus demonstrating high immunogenicity. Our observations of immunogenicity in monkeys showed that the unpurified inactivated SARS vaccine induced almost the same level of neutralizing antibody as the purified vaccine. The results indicated that the purified inactivated SARS vaccine we developed could induce high levels of neutralizing antibody, protect monkeys after a SARS-CoV challenge, and be administered safely in monkeys.

abstract:
  BACKGROUND: In 2003, severe acute respiratory syndrome (SARS) resulted in hundreds of infections and deaths globally. We aim to assess immunogenicity and protective efficacy of purified inactivated Vero-cell SARS vaccine in monkeys. METHODS: The cultures of SARS coronavirus (SARS-CoV) BJ-01 strain infected Vero cells were inactivated with β-propiolactone. Sequential procedures, including ultrafiltration, gel filtration and ion exchange chromatography, were performed to obtain purified inactivated SARS vaccine. The purified SARS vaccine was analyzed with electron microscope, HPLC and Western blotting. We immunized three groups of cynomolgus macaques fascicularis with adjuvant-containing purified vaccine, purified vaccine and unpurified vaccine, respectively, and a fourth group served as a control. Antibody titers were measured by plaque reduction neutralization test. The vaccinated monkeys were challenged with SARS-CoV BJ-01 strain to observe protective efficacy. Additionally, three groups of rhesus monkeys were immunized with different doses of the purified inactivated SARS vaccine (0.5, 1 and 2 μg/time/monkey) on days 0 and 7, and the monkeys were challenged with SARS-CoV GZ-01 strain. We assessed the safety of the SARS vaccine and observed whether the antibody dependent enhancement (ADE) occurred under low levels of neutralizing antibody in rhesus. FINDINGS: The purity of SARS vaccine was 97.6% by HPLC identification and reacted with convalescent sera of SARS patients. The purified SARS vaccine induced high levels of neutralizing antibodies and prevented the replication of SARS-CoV in monkeys. Under low levels of neutralizing antibody, no exacerbation of clinical symptoms was observed when the immunized monkeys were challenged with SARS-CoV. In this preliminary animal trial, no side effects were detected when monkeys were immunized with purified SARS vaccine either at normal or large doses. INTERPRETATION: The purified inactivated SARS vaccine could induce high levels of neutralizing antibody, and protect the monkeys from the challenge of SARS-CoV. The SARS vaccine prepared in the study appeared to be safe in monkeys.


id: cord-310249-cvv77f10
author: Yule, Terecita D.
date: 1997-05-31
txt: ./txt/cord-310249-cvv77f10.txt
cache: ./cache/cord-310249-cvv77f10.txt
extension: .txt
mime: text/plain
url: https://api.elsevier.com/content/article/pii/S0264410X96002320
doi: 10.1016/s0264-410x(96)00232-0
summary:
  In canine parvovirus infected puppies we measured the levels of acute phase proteins and changes in leukocyte phenotypes and cell trafficking by flow cytometry. In this study we evaluated whether measuring levels of acute phase proteins and investigating changes in leukocyte phenotypes by flow cytometry would complement conventional clinical assessment of a vaccine efficacy study. The association of these parameters with the major clinical signs of parvovirus induced disease in vaccinated vs nonvaccinated animals is described for seropositive puppies given a CPV-2 vaccine followed by experimental infection with CPV-2b. Low but significant SAA values were observed in three vaccinates on sporadic days post-challenge, but these values did not coincide with clinical signs, virus shed or hematologic changes. Using cell specific antibodies and flow cytometric analysis, a mean of 88% of leukocytes in peripheral Days Post CPV-2 Challenge blood were positively identified as T-cells (CD4+ and CD@, pan-T), B-cells, monocytes, and neutrophils when compared to the absolute leukocyte count obtained conventionally.

title:
  Canine parvovirus vaccine elicits protection from the inflammatory and clinical consequences of the disease

abstract:
  Abstract Inflammatory changes following infection are central to the clinical manifestation of disease. However, information regarding such changes in animal disease is limited. In canine parvovirus infected puppies we measured the levels of acute phase proteins and changes in leukocyte phenotypes and cell trafficking by flow cytometry. These parameters correlated with conventional assessment of clinical disease in a vaccine efficacy study. Seropositive (CPV-2) 6-week-old puppies given three doses of a CPV-2 containing vaccine developed significant antibody titers and remained healthy after experimental infection with CPV-2b. Unvaccinated controls developed clinical signs and shed virus. Importantly, acute phase proteins became elevated, and lymphopenia, neutropenia and modulation of neutrophil-CD4 were detected in controls but not in vaccinates.


id: cord-312517-b24zlaqt
author: Kim, Denny
date: 2020-06-19
txt: ./txt/cord-312517-b24zlaqt.txt
cache: ./cache/cord-312517-b24zlaqt.txt
extension: .txt
mime: text/plain
url: https://api.elsevier.com/content/article/pii/S0264410X20307891
doi: 10.1016/j.vaccine.2020.06.017
summary:
  title: The Brighton collaboration standardized template for collection of key information for benefit-risk assessment of nucleic acid (RNA and DNA) vaccines The Brighton Collaboration Viral Vector Vaccines Safety Working Group (V3SWG) has prepared a standardized template to describe the key considerations for the benefit-risk assessment of nucleic acid vaccines. The Brighton Collaboration formed the Viral Vector Vaccines Safety Working Group (V3SWG) in October 2008 to improve the ability of key stakeholders to anticipate potential safety issues and meaningfully assess or interpret safety data, thereby facilitating greater public acceptance when viral vector vaccines are licensed [2] . When completing information on adverse effects in Section 8, please provide as many details as possible based on the Brighton Collaboration Guidelines for collection, analysis and presentation of vaccine safety data in pre-and post-licensure clinical studies [13] .

title:
  The Brighton collaboration standardized template for collection of key information for benefit-risk assessment of nucleic acid (RNA and DNA) vaccines

abstract:
  Nucleic acid (DNA and RNA) vaccines are among the most advanced vaccines for COVID-19 under development. The Brighton Collaboration Viral Vector Vaccines Safety Working Group (V3SWG) has prepared a standardized template to describe the key considerations for the benefit-risk assessment of nucleic acid vaccines. This will facilitate the assessment by key stakeholders of potential safety issues and understanding of overall benefit-risk. The structured assessment provided by the template can also help improve communication and public acceptance of licensed nucleic acid vaccines.


id: cord-313911-lfn9ggg3
title: LC16m8: An attenuated smallpox vaccine
author: Kenner, Julie
date: 2006-11-17
txt: ./txt/cord-313911-lfn9ggg3.txt
cache: ./cache/cord-313911-lfn9ggg3.txt
extension: .txt
mime: text/plain
url: https://www.sciencedirect.com/science/article/pii/S0264410X06004142
doi: 10.1016/j.vaccine.2006.03.087
summary:
  LC16m8, an attenuated, replicating smallpox vaccine derived from the Lister strain of vaccinia, is currently licensed in Japan where it was safely used in over 50,000 children in the 1970s. LC16m8 is immunogenic after a single dose, and recent studies in two different animal models have demonstrated protective efficacy equivalent to that of the only FDA-licensed smallpox vaccine. In addition, plaque-purified LC16m8 and a construct of LC16m8 lacking the B5R gene were shown to have safety profiles comparable to that of MVA in the same animal models and to confer protective immunity in a mouse/intranasal vaccinia (Western Reserve [WR] strain) challenge study [47] . Since animal challenge studies were not conducted during the development of LC16m8 in the 1970s, alternative measures of immunity that had been used to characterize other smallpox vaccines [65, 66] were used to evaluate the efficacy of LC16m8 in early clinical trials in Japan.

abstract:
  The frequency of moderate to severe adverse reactions associated with smallpox vaccines currently stockpiled in the US, and the continued threat of bioterrorism have prompted the development of effective vaccines with improved safety profiles. LC16m8, an attenuated, replicating smallpox vaccine derived from the Lister strain of vaccinia, is currently licensed in Japan where it was safely used in over 50,000 children in the 1970s. It has been shown to have markedly less neurotoxicity than unattenuated vaccines in nonclinical studies. LC16m8 is immunogenic after a single dose, and recent studies in two different animal models have demonstrated protective efficacy equivalent to that of the only FDA-licensed smallpox vaccine. This article reviews the history and available scientific literature regarding LC16m8 and provides comparisons to other smallpox vaccines.


id: cord-315437-h6xjudm0
title: Engineering a stable CHO cell line for the expression of a MERS-coronavirus vaccine antigen
author: Nyon, Mun Peak
date: 2018-03-27
url: https://api.elsevier.com/content/article/pii/S0264410X18302524
doi: 10.1016/j.vaccine.2018.02.065
abstract:
  Abstract Middle East respiratory syndrome coronavirus (MERS-CoV) has infected at least 2040 patients and caused 712 deaths since its first appearance in 2012, yet neither pathogen-specific therapeutics nor approved vaccines are available. To address this need, we are developing a subunit recombinant protein vaccine comprising residues 377–588 of the MERS-CoV spike protein receptor-binding domain (RBD), which, when formulated with the AddaVax adjuvant, it induces a significant neutralizing antibody response and protection against MERS-CoV challenge in vaccinated animals. To prepare for the manufacture and first-in-human testing of the vaccine, we have developed a process to stably produce the recombinant MERS S377-588 protein in Chinese hamster ovary (CHO) cells. To accomplish this, we transfected an adherent dihydrofolate reductase-deficient CHO cell line (adCHO) with a plasmid encoding S377-588 fused with the human IgG Fc fragment (S377-588-Fc). We then demonstrated the interleukin-2 signal peptide-directed secretion of the recombinant protein into extracellular milieu. Using a gradually increasing methotrexate (MTX) concentration to 5 μM, we increased protein yield by a factor of 40. The adCHO-expressed S377-588-Fc recombinant protein demonstrated functionality and binding specificity identical to those of the protein from transiently transfected HEK293T cells. In addition, hCD26/dipeptidyl peptidase-4 (DPP4) transgenic mice vaccinated with AddaVax-adjuvanted S377-588-Fc could produce neutralizing antibodies against MERS-CoV and survived for at least 21 days after challenge with live MERS-CoV with no evidence of immunological toxicity or eosinophilic immune enhancement. To prepare for large scale-manufacture of the vaccine antigen, we have further developed a high-yield monoclonal suspension CHO cell line.


id: cord-316295-x636ux34
author: Roth, Bernhard
date: 2012-01-11
txt: ./txt/cord-316295-x636ux34.txt
cache: ./cache/cord-316295-x636ux34.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/22119922/
doi: 10.1016/j.vaccine.2011.11.063
summary:
  Abstract This paper summarizes results obtained by multiplex PCR screening of human clinical samples for respiratory viruses and corresponding data obtained after passaging of virus-positive samples in MDCK 33016PF cells. Using lower inoculum dilutions than those normally applied for preparations containing influenza virus (total dilution of the original sample of ∼104), the positive results for the different viruses turned negative already after 2 or 3 passages in MDCK 33016PF cells. In a similar way, samples with positive and questionable multiplex PCR results only for viruses other than influenza virus were also cultivated for 2 or 3 passages in MDCK 33016PF cells. Considering the selection of specimens, the high percentage of influenza-positive results is not surprising, but a significant number of samples (66/370 or 17.8%) also tested positive for other viruses, such as adenovirus, bocavirus, coronavirus, enterovirus, metapneumovirus (HMPV), parainfluenza virus (PIV), rhinovirus, and respiratory syncytial virus (RSV).

title:
  Isolation of influenza viruses in MDCK 33016PF cells and clearance of contaminating respiratory viruses

abstract:
  Abstract This paper summarizes results obtained by multiplex PCR screening of human clinical samples for respiratory viruses and corresponding data obtained after passaging of virus-positive samples in MDCK 33016PF cells. Using the ResPlexII v2.0 (Qiagen) multiplex PCR, 393 positive results were obtained in 468 clinical samples collected during an influenza season in Germany. The overall distribution of positive results was influenza A 42.0%, influenza B 38.7%, adenovirus 1.5%, bocavirus 0.5%, coronavirus 3.3%, enterovirus 5.6%, metapneumovirus 1.0%, parainfluenza virus 0.8%, rhinovirus 4.1%, and respiratory syncytial virus (RSV) 2.5%. Double infections of influenza virus together with another virus were found for adenovirus B and E, bocavirus, coronavirus, enterovirus and for rhinovirus. These other viruses were rapidly lost upon passages in MDCK 33016PF cells and under conditions as applied to influenza virus passaging. Clinical samples, in which no influenza virus but other viruses were found, were also subject to passages in MDCK 33016PF cells. Using lower inoculum dilutions than those normally applied for preparations containing influenza virus (total dilution of the original sample of ∼104), the positive results for the different viruses turned negative already after 2 or 3 passages in MDCK 33016PF cells. These results demonstrate that, under practical conditions as applied to grow influenza viruses, contaminating viruses can be effectively removed by passages in MDCK cells. In combination with their superior isolation efficiency, MDCK cells appear highly suitable to be used as an alternative to embryonated eggs to isolate and propagate influenza vaccine candidate viruses.


id: cord-316839-wckqscvm
title: Field evaluation of a Mycoplasma bovis bacterin in young dairy calves
author: Maunsell, Fiona P.
date: 2009-05-11
txt: ./txt/cord-316839-wckqscvm.txt
cache: ./cache/cord-316839-wckqscvm.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1016/j.vaccine.2009.02.100
doi: 10.1016/j.vaccine.2009.02.100
summary:
  Mycoplasma bovis is an important cause of pneumonia, otitis media and arthritis in young dairy calves, and there is a critical need for improved preventative strategies for this pathogen. bovis-associated disease; for calves in the remaining 2 herds, the incidence risk for respiratory disease, otitis media and arthritis from 3 to 90 days of age was 0.64, 0.28 and 0.02, respectively. bovis has emerged as an increasingly important cause of respiratory disease, otitis media and arthritis in young calves less than 3 months of age [1, 2, 6, 7, 9] . bovis-associated disease (respiratory disease, otitis media, arthritis) and mortality in dairy calves up to 90 days of age. bovis bacterin in proprietary oil-based adjuvant that had a conditional license for the prevention of respiratory disease in U.S. feeder and stocker calves at the time of the study (Texas Vet. Labs, Inc., San Angelo, TX), while the other group received a placebo (all vaccine components except antigen; control group).

abstract:
  Mycoplasma bovis is an important cause of pneumonia, otitis media and arthritis in young dairy calves, and there is a critical need for improved preventative strategies for this pathogen. We conducted a randomized, placebo-controlled, double-blinded field trial to determine the efficacy of a commercial M. bovis vaccine for the prevention of M. bovis-associated disease in calves. Calves (n = 373) on 3 Florida dairies with a history of M. bovis infection received an M. bovis bacterin or a placebo, administered subcutaneously at 3, 14 and 35 days of age. One of the herds did not experience M. bovis-associated disease; for calves in the remaining 2 herds, the incidence risk for respiratory disease, otitis media and arthritis from 3 to 90 days of age was 0.64, 0.28 and 0.02, respectively. Vaccination had no effect on the age at first treatment for M. bovis-associated disease, incidence of respiratory disease, mortality, weight gain, or nasal colonization with M. bovis in the first 90 days of life. In one herd, vaccination was associated with an increased risk of otitis media. There was no association between M. bovis-specific serum antibody titers and morbidity in vaccinated calves. Under the field conditions in this study, this vaccine was not efficacious for the prevention of M. bovis-associated disease in young dairy calves.


id: cord-317347-by8albr9
title: Age-dependent immune responses and immune protection after avian coronavirus vaccination
author: van Ginkel, Frederik W.
date: 2015-05-28
txt: ./txt/cord-317347-by8albr9.txt
cache: ./cache/cord-317347-by8albr9.txt
extension: .txt
mime: text/plain
url: https://api.elsevier.com/content/article/pii/S0264410X1500479X
doi: 10.1016/j.vaccine.2015.04.026
summary:
  The delayed and/or lower antibody response combined with lower IgG avidity indices coincided with increased tracheal inflammation and depletion of tracheal epithelia cells and goblet cells upon IBV field strain challenge. Therefore, the ability of SPF chickens of different age to induce an IBV-specific antibody response and protect against challenge with an IBV field strain was measured. In order to measure IgG (IgY), IgA and IgM antibody levels in plasma and tears of chicken, an IBV-specific enzyme-linked immunosorbent assay (ELISA) was developed as previously described [20] . These data are consistent with a delay in the IgA plasma response to IBV in birds vaccinated at a younger age and a non-significant decline in mean IgA titers in the 1-day-old group. This would be consistent with a drop of presumably natural maternal IBV-specific IgM antibodies in these SPF chickens in the day 7 control age group.

abstract:
  Infectious bronchitis virus (IBV) is an endemic disease of chickens and a major contributor to economic losses for the poultry industry despite vaccination. Recent observations indicated that chicks may have an immature immune system immediately after hatching when vaccinated for IBV. Therefore we hypothesized that early IBV vaccination will generate an immature, poorly protective IBV-specific immune response contributing to immune escape and persistence of IBV. To test this hypothesis the IBV-specific immune response and immune protection were measured in chicks vaccinated at different ages. This demonstrated a delayed production of IgG and IgA plasma antibodies in the 1, 7 and 14-day-old vaccination groups and also lower IgA antibody levels were observed in plasma of the 1-day-old group. Similar observations were made for antibodies in tears. In addition, IgG antibodies from the 1-day-old group had lower avidity indices than day 28 vaccinated birds. The delayed and/or lower antibody response combined with lower IgG avidity indices coincided with increased tracheal inflammation and depletion of tracheal epithelia cells and goblet cells upon IBV field strain challenge. The lack of vaccine-mediated protection was most pronounced in the 1-day-old vaccination group and to a lesser extent the 7-day-old group, while the 14-day-old and older chickens were protected. These data strongly support IBV vaccination after day 7 post hatch.


id: cord-318407-uy0f7f2o
author: Nara, Peter L.
date: 2008-11-18
txt: ./txt/cord-318407-uy0f7f2o.txt
cache: ./cache/cord-318407-uy0f7f2o.txt
extension: .txt
mime: text/plain
url: https://www.sciencedirect.com/science/article/pii/S0264410X08010268
doi: 10.1016/j.vaccine.2008.07.094
summary:
  For vaccination as a public health tool to have its greatest impacts in human and veterinary medicine, these great medical sciences will have to come together, policy-relevant science for sustainable conservation in developing and developed countries needs to become the norm and address poverty (including lack of basic health care) in communities affected by conservation, and to consider costs and benefits (perceived or not) affecting the well-being of all stakeholders, from the local to the multinational. For vaccination as a public health tool to have its greatest impacts in human and veterinary medicine, these great medical sciences will have to come together, policy-relevant science for sustainable conservation in developing and developed countries needs to become the norm and address poverty (including lack of basic health care) in communities affected by conservation, and to consider costs and benefits (perceived or not) affecting the well-being of all stakeholders, from the local to the multinational.

title:
  Perspectives on advancing preventative medicine through vaccinology at the comparative veterinary, human and conservation medicine interface: Not missing the opportunities

abstract:
  Abstract Vaccination has historically and remains one of the most cost-effective and safest forms of medicine today. Along with basic understanding of germ theory and sanitation, vaccination, over the past 50 years, has transformed lives and economies in both rich and poor countries by its direct impact on human and animal life—resulting in the eradication of small pox, huge reductions in the burden of previously common human and animal diseases such as polio, typhoid, measles in human medicine and contagious bovine pleuropneumonia, foot-and-mouth disease, screwworm and hog cholera and the verge of eradicating brucellosis, tuberculosis, and pseudorabies in veterinary medicine. In addition vaccination along with other animal production changes has provided the ability to produce otherwise unaffordable animal protein and animal health worldwide. The landscape however on which vaccinology was discovered and applied over the past 200 years, even in the past 10 years has and is undergoing continuous change. For vaccination as a public health tool to have its greatest impacts in human and veterinary medicine, these great medical sciences will have to come together, policy-relevant science for sustainable conservation in developing and developed countries needs to become the norm and address poverty (including lack of basic health care) in communities affected by conservation, and to consider costs and benefits (perceived or not) affecting the well-being of all stakeholders, from the local to the multinational. The need to return to and/or develop new education-based models for turning the tide from the heavily return-on-investment therapeutic era of the last century into one where the investment into the preventative sciences and medicine lead to sustainable cultural and cost-effective public health and economic changes of the future is never more evident than today. The new complex problems of the new millennium will require new educational models that train para- and professional people for thinking and solving complex inter-related biological, ecological, public-, political/economic problems. The single profession that is best positioned to impact vaccinology is Veterinary Medicine. It’s melding with human medicine and their role in future comparative and conservation-based programs will be critical to the successful application of vaccines into the 21st century.


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-322505-6q92742u
title: Evaluating the promise of recombinant transmissible vaccines
author: Basinski, Andrew J.
date: 2017-12-24
txt: ./txt/cord-322505-6q92742u.txt
cache: ./cache/cord-322505-6q92742u.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1016/j.vaccine.2017.12.037
doi: 10.1016/j.vaccine.2017.12.037
summary:
  We build a mathematical model to test whether a RTV can facilitate disease management in instances where reversion is likely to introduce the vector into the population or when the vector organism is already established in the host population, and the vector and vaccine share perfect cross-immunity. If cross-immunity between vaccine and vector exists, however, our results show that a RTV can substantially reduce the vaccination effort necessary to control or eradicate a pathogen only when continuously augmented with direct manual vaccination. Thus, if the vector organism has reached endemic levels in the population, has a larger R 0 than the pathogen, and imparts vaccine cross-immunity, the use of a RTV reduces the rate of direct vaccination required for prophylactic protection from a pathogen by a factor (4) Eq. Alternatively, if the vector organism is already circulating within the host population and vector infection imparts perfect vaccine cross-immunity, the benefits of a RTV are more modest, and require that autonomous vaccination be supplemented with continuous direct vaccination.

abstract:
  Transmissible vaccines have the potential to revolutionize infectious disease control by reducing the vaccination effort required to protect a population against a disease. Recent efforts to develop transmissible vaccines focus on recombinant transmissible vaccine designs (RTVs) because they pose reduced risk if intra-host evolution causes the vaccine to revert to its vector form. However, the shared antigenicity of the vaccine and vector may confer vaccine-immunity to hosts infected with the vector, thwarting the ability of the vaccine to spread through the population. We build a mathematical model to test whether a RTV can facilitate disease management in instances where reversion is likely to introduce the vector into the population or when the vector organism is already established in the host population, and the vector and vaccine share perfect cross-immunity. Our results show that a RTV can autonomously eradicate a pathogen, or protect a population from pathogen invasion, when cross-immunity between vaccine and vector is absent. If cross-immunity between vaccine and vector exists, however, our results show that a RTV can substantially reduce the vaccination effort necessary to control or eradicate a pathogen only when continuously augmented with direct manual vaccination. These results demonstrate that estimating the extent of cross-immunity between vector and vaccine is a critical step in RTV design, and that herpesvirus vectors showing facile reinfection and weak cross-immunity are promising.


id: cord-323540-7b2mt1a8
title: Contingent assessment of the COVID-19 vaccine
author: García, Leidy Y.
date: 2020-06-25
txt: ./txt/cord-323540-7b2mt1a8.txt
cache: ./cache/cord-323540-7b2mt1a8.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/32620375/
doi: 10.1016/j.vaccine.2020.06.068
summary:
  Therefore, the objective of this research was to estimate the individual''s willingness to pay (WTP) for a hypothetical COVID-19 vaccine and, at the same time, find the main factors that determine this valuation. The main results showed that the WTP depends on the preexistence of chronic disease ([Formula: see text]), knowledge of COVID-19 ([Formula: see text]), being sick with COVID-19 ([Formula: see text]), perception of government performance ([Formula: see text]), employment status ([Formula: see text]), income ([Formula: see text]), health care ([Formula: see text]), adaptation to quarantine with children at home ([Formula: see text] and whether the person has recovered from COVID-19 ([Formula: see text]. In the second section, the potential attributes of the vaccine and the context of contagion risk were presented; that is, we described the contingent market and asked about the WTP and the protest responses of individuals who are not willing to pay due to economic or moral reasons (15 items).

abstract:
  The COVID-19 pandemic has not only had a negative impact on people’s health and life behavior, but also on economies around the world. At the same time, laboratories and institutions are working hard to obtain a COVID-19 vaccine, which we hope will be available soon. However, there has been no assessment of whether an individual and society value ​​a vaccine monetarily, and what factors determine this value. Therefore, the objective of this research was to estimate the individual’s willingness to pay (WTP) for a hypothetical COVID-19 vaccine and, at the same time, find the main factors that determine this valuation. For this, we used the contingent valuation approach, in its single and double-bounded dichotomous choice format, which was based on a hypothetical market for a vaccine. The sample used was obtained through an online survey of n = 566 individuals from Chile. The main results showed that the WTP depends on the preexistence of chronic disease ([Formula: see text]), knowledge of COVID-19 ([Formula: see text]), being sick with COVID-19 ([Formula: see text]), perception of government performance ([Formula: see text]), employment status ([Formula: see text]), income ([Formula: see text]), health care ([Formula: see text]), adaptation to quarantine with children at home ([Formula: see text] and whether the person has recovered from COVID-19 ([Formula: see text]. According to our discrete choice model in double-bounded dichotomous format, it was concluded that the individuals’ WTP is US$184.72 (CI: 165.52-203.92; p < 0.01). This implies a social valuation of approximately US$2,232 million, corresponding to 1.09% of the GNP per capita.


id: cord-324911-6s7ubbxl
author: Drury, Georgina
date: 2019-04-17
url: https://www.sciencedirect.com/science/article/pii/S0264410X19301264
doi: 10.1016/j.vaccine.2019.01.050
title:
  Process mapping of vaccines: Understanding the limitations in current response to emerging epidemic threats

abstract:
  Vaccination remains the most successful and effective mechanism of pathogen control. However, their development and deployment in epidemic settings have been limited, and the 2015 Ebola outbreak in West Africa identified several bottlenecks linked to a lack of investment in pathogen research, infrastructure or regulation. Shortly after this outbreak, the UK Government established the UK Vaccine Network to ensure the UK is better prepared to respond to pathogens outbreaks of epidemic potential. As part of their work, the network commissioned the creation of a Vaccine Development Tool (http://www.vaccinedevelopment.org.uk/) to serve as a guide to the key stages in vaccine development. The tool also set out to capture the key, rate-limiting bottlenecks in the development of vaccines against emerging infectious disease such that corrective action could be taken, be it through research, funding, infrastructure and policy, both in the UK and internationally. The main research bottlenecks were related to understanding pathogen biology, identification of appropriate animal models and investment in the manufacturing sciences, especially into process development. Infrastructure gaps in GMP manufacturing and fill-finish were also identified and limitations in GMO regulation and regulatory and ethical approvals, especially for outbreak pathogens required new policy initiatives. The UK Vaccine Network has since begun work to correct for these limitations with a series of funding calls and development programmes. This paper seeks to summarise the Vaccine Development Tool and its key findings.


id: cord-325998-87l6nixc
title: Activation of toll-like receptor signaling pathway for protection against influenza virus infection
author: Wong, J.P.
date: 2009-05-26
txt: ./txt/cord-325998-87l6nixc.txt
cache: ./cache/cord-325998-87l6nixc.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/19200852/
doi: 10.1016/j.vaccine.2009.01.048
summary:
  This study aims to evaluate the antiviral role of nucleic acid-based agonists for the activation of toll-like receptor (TLR) signaling pathways, and its protective role in respiratory influenza A virus infections. Intranasal pre-treatment of mice with Poly ICLC and LE Poly ICLC provided high level of protection against lethal challenge with a highly lethal avian H5N1 influenza (HPAI) strain (A/H5N1/chicken/Henan clade 2), and against lethal seasonal influenza A/PR/8/34 [H1N1] and A/Aichi/2 [H3N2] virus strains. Since TLR-3 activation by ds RNA results in induction of type I interferons, it follows that Poly ICLC, when delivered in liposomes to the endosomal membrane location, may strengthen the host antiviral defence against influenza virus by priming the interferon levels and, therefore, reversing the interferon knockdown by the viruses. The effect of poly ICLC and LE Poly ICLC on the TLR-3 expression in the lungs of mice intranasally pre-treated with these drugs were determined by RT-PCR (Fig. 1) .

abstract:
  This study aims to evaluate the antiviral role of nucleic acid-based agonists for the activation of toll-like receptor (TLR) signaling pathways, and its protective role in respiratory influenza A virus infections. TLR-3 is expressed on myeloid dendritic cells, respiratory epithelium, and macrophages, and appears to play a central role in mediating both the antiviral and inflammatory responses of the innate immunity in combating viral infections. Influenza viruses can effectively inhibit the host's ability to produce interferons, and thereby suppress the immune system's antiviral defence mechanisms. Poly ICLC is a synthetic double stranded RNA comprising of polyriboinosinic-poly ribocytidylic acid (Poly IC) stabilized with l-lysine (L) and carboxymethylcellulose (C). Poly ICLC and liposome-encapsulated Poly ICLC (LE Poly ICLC) are TLR-3 agonists and are potent inducer of interferons and natural killer cells. Intranasal pre-treatment of mice with Poly ICLC and LE Poly ICLC provided high level of protection against lethal challenge with a highly lethal avian H5N1 influenza (HPAI) strain (A/H5N1/chicken/Henan clade 2), and against lethal seasonal influenza A/PR/8/34 [H1N1] and A/Aichi/2 [H3N2] virus strains. The duration of protective antiviral immunity to multiple lethal doses of influenza virus A/PR/8/34 virus had been previously found to persist for up to 3 weeks in mice for LE Poly ICLC and 2 weeks for Poly ICLC. Similarly, pre-treatment of mice with CpG oligonucleotides (TLR-9 agonist) was also found to provide complete protection against influenza A/PR/8/34 infection in mice. RT-PCR analysis of lung tissues of mice treated with Poly ICLC and LE Poly ICLC revealed upregulation of TLR-3 mRNAs gene expression. Taken together, these results do support the potential role of TLR-3 and TLR-9 agonists such as Poly ICLC and LE Poly ICLC in protection against lethal seasonal and HPAI virus infection.


id: cord-328698-eeg1k5a6
author: Detoc, Maëlle
date: 2020-09-17
txt: ./txt/cord-328698-eeg1k5a6.txt
cache: ./cache/cord-328698-eeg1k5a6.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1016/j.vaccine.2020.09.041
doi: 10.1016/j.vaccine.2020.09.041
summary:
  Older age, male gender, fear about COVID-19, being a healthcare worker and individual perceived risk were associated with COVID-19 vaccine acceptance. Older age, male gender, being a healthcare worker and individual perceived risk were associated with potential acceptance to participate in a COVID-19 vaccine clinical trial. In multivariable analysis, older age, male gender, fear about COVID-19, be healthcare workers and individual perceived risk remained associated with COVID-19 vaccine acceptance. However, individuals who considered themselves at-risk for COVID-19 infection were more prone to accept to participate in a clinical trial for a vaccine. This observation suggests that in the pandemics context, individuals are more prone to participate in a clinical trial for a vaccine. However, a greater proportion of respondents to our survey declared they had been vaccinated against 2009 H1N1 pandemic influenza, so this observation may suggest that the respondents are more pro-vaccine than the general population in France, and more often healthcare workers.

title:
  Intention to participate in a COVID-19 vaccine clinical trial and to get vaccinated against COVID-19 in France during the pandemic

abstract:
  Introduction The world is facing the COVID-19 pandemic. The development of a vaccine is challenging. We aimed to determine the proportion of people who intend to get vaccinated against COVID-19 in France or to participate in a vaccine clinical trial. Methods We conducted an anonymous on-line survey from the 26th of March to the 20th of April 2020. Primary endpoints were the intention to get vaccinated against COVID-19 if a vaccine was available or participate in a vaccine clinical trial. Results Three thousand two hundred and fifty nine individuals answered the survey; women accounted for 67.4 % of the respondents. According to their statements, 2.512 participants (77.6%, 95 % CI 76.2-79 %) will certainly or probably agree to get vaccinated against COVID-19. Older age, male gender, fear about COVID-19, being a healthcare worker and individual perceived risk were associated with COVID-19 vaccine acceptance. Vaccine hesitancy was associated with a decrease in COVID-19 vaccine acceptance. One thousand and five hundred and fifty respondents (47.6 % 95 % CI 45.9-49.3 %) will certainly or probably agree to participate in a COVID-19 vaccine clinical trial. Older age, male gender, being a healthcare worker and individual perceived risk were associated with potential acceptance to participate in a COVID-19 vaccine clinical trial. Vaccine hesitancy was associated with refusal for participation in a COVID-19 vaccine clinical trial. Conclusions Nearly 75 % and 48 % of the survey respondents were respectively likely to accept vaccination or participation in a clinical trial against COVID-19. Vaccine hesitancy will be the major barrier to COVID-19 vaccine uptake.


id: cord-330406-a1tvcgqj
title: A space–time cluster of adverse events associated with canine rabies vaccine
author: Moore, George E.
date: 2005-12-01
txt: ./txt/cord-330406-a1tvcgqj.txt
cache: ./cache/cord-330406-a1tvcgqj.txt
extension: .txt
mime: text/plain
url: https://www.sciencedirect.com/science/article/pii/S0264410X05007048
doi: 10.1016/j.vaccine.2005.07.041
summary:
  Patient risk factors and/or practice vaccination protocols may therefore influence the occurrence and potential clustering of reported VAEs. The purpose of this study was to determine if practitioner-diagnosed adverse events occurring within 3 days of canine rabies vaccine administration are clustered in space and time. In time-and-space, a significant cluster of VAE was also identified; the spatial window was not altered but the cylindrical window was reduced compared to temporal analyses alone ( Table 1) Analyses of MHG populations with adjustments for patient covariates did not alter the space-time dimensions of the most likely cluster, although the adjustment for the number of concurrently administered vaccines caused the greatest reduction (3.3%) in the ratio of observed-to-expected cases ( Table 2 ). Supportive evidence for the contribution of cases by these hospitals was indicated when space-time cluster analysis, using a Poisson model with hospital-based populations and VAE rate data adjusted for number of concurrent vaccinations, identified a significant (P = 0.001) cluster of VAE involving the same 2 hospitals during a 6-month period of September 2002 through February 2003.

abstract:
  Electronic medical records of a large veterinary practice were used for surveillance of potential space–time clustering of adverse events associated with rabies vaccination in dogs. The study population was 257,564 dogs vaccinated in 169 hospitals in 13 US metropolitan areas during a 24-month period. Using a scan statistic for population rate data, significant space–time clusters were identified involving the Atlanta and Tampa/St. Petersburg areas during a 4-month period. Separate spatial–temporal analyses of these cities using coordinates for individual address coordinates identified one significant patient cluster (P = 0.002), associated with a 23.26 km-radius area in Atlanta (20 adverse events in 702 dogs; 2.85%) from November 2002 through February 2003. This percentage of adverse events was significantly increased after adjustment for host-related factors and the number of concurrent vaccinations.


id: cord-331900-xtwqv4fk
author: Hussain, Althaf I.
date: 2010-05-14
url: https://www.ncbi.nlm.nih.gov/pubmed/20307595/
doi: 10.1016/j.vaccine.2010.03.005
title:
  Comparison of egg and high yielding MDCK cell-derived live attenuated influenza virus for commercial production of trivalent influenza vaccine: In vitro cell susceptibility and influenza virus replication kinetics in permissive and semi-permissive cells()

abstract:
  Currently MedImmune manufactures cold-adapted (ca) live, attenuated influenza vaccine (LAIV) from specific-pathogen free (SPF) chicken eggs. Difficulties in production scale-up and potential exposure of chicken flocks to avian influenza viruses especially in the event of a pandemic influenza outbreak have prompted evaluation and development of alternative non-egg based influenza vaccine manufacturing technologies. As part of MedImmune's effort to develop the live attenuated influenza vaccine (LAIV) using cell culture production technologies we have investigated the use of high yielding, cloned MDCK cells as a substrate for vaccine production by assessing host range and virus replication of influenza virus produced from both SPF egg and MDCK cell production technologies. In addition to cloned MDCK cells the indicator cell lines used to evaluate the impact of producing LAIV in cells on host range and replication included two human cell lines: human lung carcinoma (A549) cells and human muco-epidermoid bronchiolar carcinoma (NCI H292) cells. The influenza viruses used to infect the indicators cell lines represented both the egg and cell culture manufacturing processes and included virus strains that composed the 2006–2007 influenza seasonal trivalent vaccine (A/New Caledonia/20/99 (H1N1), A/Wisconsin/67/05 (H3N2) and B/Malaysia/2506/04). Results from this study demonstrate remarkable similarity between influenza viruses representing the current commercial egg produced and developmental MDCK cell produced vaccine production platforms. MedImmune's high yielding cloned MDCK cells used for the cell culture based vaccine production were highly permissive to both egg and cell produced ca attenuated influenza viruses. Both the A549 and NCI H292 cells regardless of production system were less permissive to influenza A and B viruses than the MDCK cells. Irrespective of the indicator cell line used the replication properties were similar between egg and the cell produced influenza viruses. Based on these study results we conclude that the MDCK cell produced and egg produced vaccine strains are highly comparable.


id: cord-332358-0t4uxmj2
author: Lamphear, Barry J.
date: 2004-06-23
txt: ./txt/cord-332358-0t4uxmj2.txt
cache: ./cache/cord-332358-0t4uxmj2.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/15193404/
doi: 10.1016/j.vaccine.2003.11.066
summary:
  The modified live virus vaccine, which was administered twice orally and then once intramuscularly resulted in gilts in all groups having similar TGEV serum neutralizing titers 35 days prior to farrowing. Analysis of serum samples taken from gilts at 14 days prior to farrowing showed that animals that had received the oral corn-based TGEV vaccine (groups A-C) had notably higher serum neutralization titers than those that had received no material at this stage (groups D and F). Although more oral administrations of the corn-based vaccine appeared to increase the neutralization titer, differences between the treatment groups (A-C) were not significant and none of the treatments induced a significantly stronger response than the intramuscular boost of modified live vaccine delivered to group E. The orally administered corn-based TGEV vaccine is effective in boosting the serum neutralizing titer response in animals previously sensitized to TGEV using the modified live virus vaccine.

title:
  A corn-based delivery system for animal vaccines: an oral transmissible gastroenteritis virus vaccine boosts lactogenic immunity in swine

abstract:
  Recombinant plant expression systems offer a means to produce large quantities of selected antigens for subunit vaccines. Cereals are particularly well-suited expression vehicles since the expressed proteins can be stored at relatively high concentrations for extended periods of time without degradation and dry seed can be formulated into oral vaccines suitable for commercial applications. A subunit vaccine candidate directed against porcine transmissible gastroenteritis virus and expressed in corn seed has been developed for oral delivery to swine. Here, we show that this vaccine, when administered to previously sensitized gilts, can boost neutralizing antibody levels in the animals’ serum, colostrum and milk. Thus, this vaccine candidate is effective at boosting lactogenic immunity and is appropriate to pursue through large-scale field trials preceding commercialization.


id: cord-336730-hqgwj8vs
author: Fehr, Daniela
date: 1997-07-31
url: https://api.elsevier.com/content/article/pii/S0264410X97000066
doi: 10.1016/s0264-410x(97)00006-6
title:
  Placebo-controlled evaluation of a modified life virus vaccine against feline infectious peritonitis: safety and efficacy under field conditions

abstract:
  Abstract A modified live virus vaccine against feline infectious peritonitis (FIP) was evaluated in a double blind, placebo-controlled field trial in two high-risk populations. The vaccine was found to be safe and efficacious in one population of cats that had low antibody titre against feline coronavirus (FCoV) at the time of vaccination. Although clinically healthy at the time of vaccination, retrospectively some vaccinees that later came down with FIP were found to be RT-PCR positive for FCoV in plasma and showed changes in blood parameters consistent with early stage of FIP. It is concluded that vaccination can protect cats with no or low FCoV antibody titres and that in some cats vaccine failure was probably due to pre-existing infection.


id: cord-339070-jnmogy7s
title: Influenza associated mortality in the subtropics and tropics: Results from three Asian cities
author: Yang, Lin
date: 2011-11-08
txt: ./txt/cord-339070-jnmogy7s.txt
cache: ./cache/cord-339070-jnmogy7s.txt
extension: .txt
mime: text/plain
url: https://www.sciencedirect.com/science/article/pii/S0264410X11014903
doi: 10.1016/j.vaccine.2011.09.071
summary:
  In this study, we applied a standardized modeling strategy to the mortality and virology data from three Asian cities: subtropical Guangzhou and Hong Kong, and tropical Singapore, to estimate the disease burden of influenza in these cities. Mortality data for each city were obtained from Hong Kong Census and Statistics Department (coded according to the International Classification of Diseases Tenth Revision, ICD-10), Guangzhou Department of Health (coded in ICD-10) and Singapore Registry of Births and Deaths (coded in ICD-9), respectively. The present study adopted a standardized modeling approach to show that the overall influenza burden was comparable between the two subtropical cities Guangzhou and Hong Kong, but lower in the tropical Singapore. Annual excess all-cause mortality rates associated with influenza (per 100,000 population) between Guangzhou, Hong Kong and Singapore, all-ages group.

abstract:
  Influenza has been well documented to significantly contribute to winter increase of mortality in the temperate countries, but its severity in the subtropics and tropics was not recognized until recently and geographical variations of disease burden in these regions remain poorly understood. In this study, we applied a standardized modeling strategy to the mortality and virology data from three Asian cities: subtropical Guangzhou and Hong Kong, and tropical Singapore, to estimate the disease burden of influenza in these cities. We found that influenza was associated with 10.6, 13.4 and 8.3 deaths per 100,000 population in Guangzhou, Hong Kong and Singapore, respectively. The annual rates of excess deaths in the elders were estimated highest in Guangzhou and lowest in Singapore. The excess death rate attributable to A/H1N1 subtype was found slightly higher than the rates attributable to A/H3N2 during the study period of 2004–2006 based on the data from Hong Kong and Guangzhou. Our study revealed a geographical variation in the disease burden of influenza in these subtropical and tropical cities. These results highlight a need to explore the determinants for severity of seasonal influenza.


id: cord-340686-uq0fsqh3
author: Dwivedi, Varun
date: 2011-05-23
txt: ./txt/cord-340686-uq0fsqh3.txt
cache: ./cache/cord-340686-uq0fsqh3.txt
extension: .txt
mime: text/plain
url: https://api.elsevier.com/content/article/pii/S0264410X11003574
doi: 10.1016/j.vaccine.2011.03.005
summary:
  title: 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 In the present study, mucosal adjuvanticity of Mycobacterium tuberculosis whole cell lysate (Mtb WCL) was evaluated in pigs administered a modified live PRRS virus vaccine (PRRS-MLV) intranasally. Importantly, an increased and early generation of PRRSV specific neutralizing antibodies were detected in PRRS-MLV+ Mtb WCL compared to pigs inoculated with vaccine alone. An increased immunosuppressive cytokine response was associated with a significant increase in the frequency of T-regulatory cells (Tregs) in the lungs of pigs receiving PRRS-MLV compared to pigs inoculated with PRRS-MLV+ Mtb WCL (Fig. 1D) . In addition, increased (but not significant) frequency of ␥␦ T cells in the lungs of PRRS-MLV+ Mtb WCL vaccinated pigs was detected at all the PID (Table 2D ).

title:
  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:
  Porcine reproductive and respiratory syndrome (PRRS) is an economically important disease to pork producers worldwide. Commercially, both live and killed PRRSV vaccines are available to control PRRS, but they are not always successful. Based on the results of mucosal immunization studies in other viral models, a good mucosal vaccine may be an effective way to elicit protective immunity to control PRRS outbreaks. In the present study, mucosal adjuvanticity of Mycobacterium tuberculosis whole cell lysate (Mtb WCL) was evaluated in pigs administered a modified live PRRS virus vaccine (PRRS-MLV) intranasally. A Mtb WCL mediated increase in the frequency of NK cells, CD8(+)and CD4(+) T cells, and γδ T cells in pig lungs were detected. Importantly, an increased and early generation of PRRSV specific neutralizing antibodies were detected in PRRS-MLV+ Mtb WCL compared to pigs inoculated with vaccine alone. In addition, there was an increased secretion of Th1 cytokines (IFNγ and IL-12) that correlated with a reciprocal reduction in the production of immunosuppressive cytokines (IL-10 and TGFβ) as well as T-regulatory cells in pigs vaccinated with PRRS-MLV+ Mtb WCL. Further, a complete rescue in arginase levels in the lungs mediated through Mtb WCL was observed in pigs inoculated with PRRS-MLV. In conclusion, Mtb WCL may be a potent mucosal adjuvant for PRRS-MLV in order to potentiate the anti-PRRSV specific immune responses to control PRRS effectively.


id: cord-341626-04svm6le
author: Assink, M.D.M.
date: 2009-02-11
url: https://doi.org/10.1016/j.vaccine.2008.11.070
doi: 10.1016/j.vaccine.2008.11.070
title:
  Excess drug prescriptions during influenza and RSV seasons in the Netherlands: Potential implications for extended influenza vaccination

abstract:
  Influenza and respiratory syncytial virus (RSV) infections are responsible for considerable morbidity, mortality and health-care resource use. For the Netherlands, we estimated age and risk-group specific numbers of antibiotics, otologicals and cardiovascular prescriptions per 10,000 person-years during periods with elevated activity of influenza or RSV, and compared these with peri-season rates. Data were taken from the University of Groningen in-house prescription database (www.iadb.nl) and virological surveillance for the period 1998–2006. During influenza and RSV periods excess antibiotic prescriptions were estimated for all age groups. In the age groups 0–1 and 2–4 years, excess antibiotic prescriptions during periods with elevated RSV activity (65% and 59% of peri-seasonal rates) exceeded the surpluses estimated during the influenza-activity periods (24% and 34% of peri-seasonal rates) while for otologicals excess prescriptions were higher for influenza (22% and 27%) than for RSV (14% and 17%). Among persons of 50 years and older, notably those without medical high-risk conditions, excess prescriptions for cardiovascular medications were estimated during the influenza periods at approximately 10% (this was also already seen in persons aged 45–49). Our results may have implications for influenza vaccination policies. In particular, extension of influenza vaccination to groups of non-elderly adults and young children may lower excess prescriptions during these influenza periods for all three types of drug prescriptions investigated.


id: cord-341970-pho6dksc
title: Immunization with SARS-CoV S DNA vaccine generates memory CD4(+) and CD8(+) T cell immune responses
author: Huang, Jun
date: 2006-06-05
url: https://www.ncbi.nlm.nih.gov/pubmed/16621188/
doi: 10.1016/j.vaccine.2006.03.058
abstract:
  An effective vaccine for severe acute respiratory syndrome (SARS) will probably require the generation and maintenance of both humoral and cellular immune responses. It has been reported that after natural infection in humans and immunization in animals with SARS-CoV vaccine, antibody is produced and persistent for a long period of time. In the present study, mice were immunized i.m. with SARS-CoV S DNA vaccine, and three different methods (ELISA, ELISPOT and FACS) were used to evaluate the immune responses when the cells were stimulated in vitro with a pool of peptides overlapping entire SARS spike protein. The results show that prime-immunization with SARS-CoV S DNA vaccine can induce both CD4(+) and CD8(+) T cell responses. Boosting with the same vaccine enhances CD4(+) and CD8(+) T cell responses in both lymphoid and nonlymphoid organs and were persistent over two months. The SARS-CoV S-specific CD4(+) and CD8(+) T cells were CD62L(−), a marker for memory cells, and −30 to 50% of the cells expressed IL-7Rα (CD127), a marker for the capacity of effector cells to develop into memory cells. In addition, immunization with the DNA vaccine elicited high levels of antibody production. Taken together, these data demonstrate that immunization with SARS-CoV S DNA vaccine can generate antigen-specific humoral and cellular immune responses that may contribute to long-term protection.


id: cord-342405-nsj9dh48
title: India’s cost-effective COVID-19 vaccine development initiatives
author: Chakraborty, Chiranjib
date: 2020-10-20
txt: ./txt/cord-342405-nsj9dh48.txt
cache: ./cache/cord-342405-nsj9dh48.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1016/j.vaccine.2020.10.056
doi: 10.1016/j.vaccine.2020.10.056
abstract: nan
summary:
  title: India''s cost-effective COVID-19 vaccine development initiatives In addition, millions of people who live across over 30 world''s poorest countries will also expect the affordable low-cost vaccine. It''s currently collaborating with Codagenix to develop a vaccine, including live-attenuated vaccine against COVID-19. 6 Besides, it has a partnership with Codagenix, a New York based firm specialized on vaccines and the Oxford University to produce the COVID-19 vaccine. 10 What''s unique about India is that it has the expertise for low-cost per-unit vaccine production of vaccines. Due to the low cost vaccine making history, new products against COVID-19 will be of great use in over 30 low-income countries worldwide benefiting millions of people who cannot afford expensive vaccines. Few months ago, the WHO has praised India''s vaccine production capacity in a meeting of COVID-19. It''s time for the developing world to collaborate with India to produce and distribute the cost-effective COVID-19 vaccine as soon as possible.


id: cord-342831-4qfe8kok
title: Chitosan-based mucosal adjuvants: Sunrise on the ocean
author: Xia, Yufei
date: 2015-11-04
url: https://api.elsevier.com/content/article/pii/S0264410X15011056
doi: 10.1016/j.vaccine.2015.07.101
abstract:
  Mucosal vaccination, which is shown to elicit systemic and mucosal immune responses, serves as a non-invasive and convenient alternative to parenteral administration, with stronger capability in combatting diseases at the site of entry. The exploration of potent mucosal adjuvants is emerging as a significant area, based on the continued necessity to amplify the immune responses to a wide array of antigens that are poorly immunogenic at the mucosal sites. As one of the inspirations from the ocean, chitosan-based mucosal adjuvants have been developed with unique advantages, such as, ability of mucosal adhesion, distinct trait of opening the junctions to allow the paracellular transport of antigen, good tolerability and biocompatibility, which guaranteed the great potential in capitalizing on their application in human clinical trials. In this review, the state of art of chitosan and its derivatives as mucosal adjuvants, including thermo-sensitive chitosan system as mucosal adjuvant that were newly developed by author's group, was described, as well as the clinical application perspective. After a brief introduction of mucosal adjuvants, chitosan and its derivatives as robust immune potentiator were discussed in detail and depth, in regard to the metabolism, safety profile, mode of actions and preclinical and clinical applications, which may shed light on the massive clinical application of chitosan as mucosal adjuvant.


id: cord-344316-mwnnmwnw
author: Herst, C.V.
date: 2020-04-28
url: https://www.ncbi.nlm.nih.gov/pubmed/32418793/
doi: 10.1016/j.vaccine.2020.04.034
title:
  An Effective CTL Peptide Vaccine for Ebola Zaire Based on Survivors’ CD8+ Targeting of a Particular Nucleocapsid Protein Epitope with Potential Implications for COVID-19 Vaccine Design

abstract:
  The 2013-2016 West Africa EBOV epidemic was the biggest EBOV outbreak to date. An analysis of virus-specific CD8+ T-cell immunity in 30 survivors showed that 26 of those individuals had a CD8+ response to at least one EBOV protein. The dominant response (25/26 subjects) was specific to the EBOV nucleocapsid protein (NP). It has been suggested that epitopes on the EBOV NP could form an important part of an effective T-cell vaccine for Ebola Zaire. We show that a 9-amino-acid peptide NP44-52 (YQVNNLEEI) located in a conserved region of EBOV NP provides protection against morbidity and mortality after mouse adapted EBOV challenge. A single vaccination in a C57BL/6 mouse using an adjuvanted microsphere peptide vaccine formulation containing NP44-52 is enough to confer immunity in mice. Our work suggests that a peptide vaccine based on CD8+ T-cell immunity in EBOV survivors is conceptually sound and feasible. Nucleocapsid proteins within SARS-CoV-2 contain multiple class I epitopes with predicted HLA restrictions consistent with broad population coverage. A similar approach to a CTL vaccine design may be possible for that virus.


id: cord-345191-nabxpyw3
author: Bell, Sadie
date: 2020-10-19
url: https://www.ncbi.nlm.nih.gov/pubmed/33109389/
doi: 10.1016/j.vaccine.2020.10.027
title:
  Parents’ and guardians’ views on the acceptability of a future COVID-19 vaccine: a multi-methods study in England

abstract:
  Background The availability of a COVID-19 vaccine has been heralded as key to controlling the COVID-19 pandemic. COVID-19 vaccination programme success will rely on public willingness to be vaccinated. Methods We used a multi-methods approach - involving an online cross-sectional survey and semi-structured interviews - to investigate parents’ and guardians’ views on the acceptability of a future COVID-19 vaccine. 1252 parents and guardians (aged 16+ years) who reported living in England with a child aged 18 months or under completed the survey. Nineteen survey participants were interviewed. Findings Most survey participants reported they would likely accept a COVID-19 vaccine for themselves (Definitely 55.8%; Unsure but leaning towards yes 34.3%) and their child/children (Definitely 48.2%; Unsure but leaning towards yes 40.9%). Less than 4% of survey participants reported that they would definitely not accept a COVID-19 vaccine. Survey participants were more likely to accept a COVID-19 vaccine for themselves than their child/children. Participants that self-reported as Black, Asian, Chinese, Mixed or Other ethnicity were almost 3 times more likely to reject a COVID-19 vaccine for themselves and their children than White British, White Irish and White Other participants. Survey participants from lower-income households were also more likely to reject a COVID-19 vaccine. In open-text survey responses and interviews, self-protection from COVID-19 was reported as the main reason for vaccine acceptance. Common concerns identified in open-text responses and interviews were around COVID-19 vaccine safety and effectiveness, mostly prompted by the newness and rapid development of the vaccine. Conclusion Information on how COVID-19 vaccines are developed and tested, including their safety and efficacy, must be communicated clearly to the public. To prevent inequalities in uptake, it is crucial to understand and address factors that may affect COVID-19 vaccine acceptability in ethnic minority and lower-income groups who are disproportionately affected by COVID-19.


id: cord-345658-u9vgycib
author: Volkmann, Ariane
date: 2020-10-17
url: https://api.elsevier.com/content/article/pii/S0264410X20310914
doi: 10.1016/j.vaccine.2020.08.050
title:
  The Brighton Collaboration standardized template for collection of key information for risk/benefit assessment of a Modified Vaccinia Ankara (MVA) vaccine platform

abstract:
  The Brighton Collaboration Viral Vector Vaccines Safety Working Group (V3SWG) was formed to evaluate the safety and characteristics of live, recombinant viral vector vaccines. The Modified Vaccinia Ankara (MVA) vector system is being explored as a platform for development of multiple vaccines. This paper reviews the molecular and biological features specifically of the MVA-BN vector system, followed by a template with details on the safety and characteristics of an MVA-BN based vaccine against Zaire ebolavirus and other filovirus strains. The MVA-BN-Filo vaccine is based on a live, highly attenuated poxviral vector incapable of replicating in human cells and encodes glycoproteins of Ebola virus Zaire, Sudan virus and Marburg virus and the nucleoprotein of the Thai Forest virus. This vaccine has been approved in the European Union in July 2020 as part of a heterologous Ebola vaccination regimen. The MVA-BN vector is attenuated following over 500 serial passages in eggs, showing restricted host tropism and incompetence to replicate in human cells. MVA has six major deletions and other mutations of genes outside these deletions, which all contribute to the replication deficiency in human and other mammalian cells. Attenuation of MVA-BN was demonstrated by safe administration in immunocompromised mice and non-human primates. In multiple clinical trials with the MVA-BN backbone, more than 7800 participants have been vaccinated, demonstrating a safety profile consistent with other licensed, modern vaccines. MVA-BN has been approved as smallpox vaccine in Europe and Canada in 2013, and as smallpox and monkeypox vaccine in the US in 2019. No signal for inflammatory cardiac disorders was identified throughout the MVA-BN development program. This is in sharp contrast to the older, replicating vaccinia smallpox vaccines, which have a known risk for myocarditis and/or pericarditis in up to 1 in 200 vaccinees. MVA-BN-Filo as part of a heterologous Ebola vaccination regimen (Ad26.ZEBOV/MVA-BN-Filo) has undergone clinical testing including Phase III in West Africa and is currently in use in large scale vaccination studies in Central African countries. This paper provides a comprehensive picture of the MVA-BN vector, which has reached regulatory approvals, both as MVA-BN backbone for smallpox/monkeypox, as well as for the MVA-BN-Filo construct as part of an Ebola vaccination regimen, and therefore aims to provide solutions to prevent disease from high-consequence human pathogens.


id: cord-346032-188gnf8j
author: Cheung, Ying-Kit
date: 2007-08-10
txt: ./txt/cord-346032-188gnf8j.txt
cache: ./cache/cord-346032-188gnf8j.txt
extension: .txt
mime: text/plain
url: https://api.elsevier.com/content/article/pii/S0264410X07005932
doi: 10.1016/j.vaccine.2007.05.025
summary:
  title: Induction of T-cell response by a DNA vaccine encoding a novel HLA-A*0201 severe acute respiratory syndrome coronavirus epitope The severe acute respiratory syndrome coronavirus nucleocapsid protein (SARS-CoV N) is one of the major targets for SARS vaccine due to its high potency in triggering immune responses. The results of the T-cell stimulation assay demonstrated that the novel N-protein peptide revealed in the present study is able to trigger specific cytotoxic T-cell response in human PBMCs. The four most immunogenic peptides (N220, N223, N227 and N317) selected in the T2-cell binding assay and the human T-cell stimulation assay were further tested for their potency in triggering immune response against the SARS N-protein expressing cells in an animal model. A peptide sequence useful for inducing the cytotoxic T-cell response should be presented as endogenous peptide epitope through proteasome digestion and have a high binding affinity towards the human MHC class I molecules.

title:
  Induction of T-cell response by a DNA vaccine encoding a novel HLA-A*0201 severe acute respiratory syndrome coronavirus epitope

abstract:
  The severe acute respiratory syndrome coronavirus nucleocapsid protein (SARS-CoV N) is one of the major targets for SARS vaccine due to its high potency in triggering immune responses. In this study, we have identified a novel HLA-A*0201 restricted epitope, N220 (LALLLLDRL), of the SARS-CoV N-protein through bioinformatics analysis. The N-protein peptide N220 shows a high binding affinity towards human MHC class I in T2-cells, and is capable of activating cytotoxic T-cells in human peripheral blood mononuclear cells (PBMCs). The application of using the N220 peptide sequence with a single-chain-trimer (SCT) approach to produce a potential DNA vaccine candidate was investigated in HLA-A2.1K(b) transgenic mice. Cytotoxicity assay clearly showed that the T-cells obtained from the vaccinated animals were able to kill the N-protein expressing cells with a cytotoxicity level of 86% in an effector cells/target cells ratio of 81:1 one week after the last vaccination, which is significantly higher than other N-protein peptides previously described. The novel immunogenic N-protein peptide revealed in the present study provides valuable information for therapeutic SARS vaccine design.


id: cord-348218-wyy4rvqb
author: Ashwell, Douglas
date: 2020-07-09
url: https://doi.org/10.1016/j.vaccine.2020.06.070
doi: 10.1016/j.vaccine.2020.06.070
title:
  When being positive might be negative: An analysis of Australian and New Zealand newspaper framing of vaccination post Australia's No Jab No Pay legislation

abstract:
  Vaccination rates are an ongoing global concern. Many developing and developed countries have rates of vaccination below rates required for herd immunity, for differing reasons. One way in which to communicate information about vaccination to the wider public is via the use of the news media. Communication agenda-setting and framing theory generally hold that the news media sets the issues of importance to society and also tells us how we should think about those issues. Emphasis framing theory however, would suggest that positively-framed statements in the media may actually be viewed as persuasive in a coercing way, leading to resistance to the messages. Further, this theory claims that negative news media is viewed as more credible and therefore, more easily accepted. We were interested to explore the framing of news reports about vaccination and the potential effects this framing may have had on the wider public over the years 2016–2017 in both Australia and New Zealand (when changes in vaccination policy and publicity respectively were on the agenda). We undertook a content analysis of 197 articles and emphasis frame, type of message, and other variables recorded. In both Australia and New Zealand, the news media messages were predominately positively framed and yet the vaccination rates of New Zealand particularly (where no policy changes mandating vaccination took place) have been decreasing. We suggest the media emphasis on positive vaccination reporting may be having the opposite effect of engendering resistance to vaccination within those who are vaccine-hesitant.


id: cord-349309-7xsbpid7
author: Condit, Richard C
date: 2020-09-06
url: https://www.sciencedirect.com/science/article/pii/S0264410X20310306
doi: 10.1016/j.vaccine.2020.08.009
title:
  The Brighton Collaboration standardized template for collection of key information for benefit-risk assessment of viral vector vaccines

abstract:
  Many of the vaccines under development for COVID-19 involve the use of viral vectors. The Brighton Collaboration Benefit-Risk Assessment of Vaccines by Technology (BRAVATO, formerly the Viral Vector Vaccine Safety Working Group, V3SWG) working group has prepared a standardized template to describe the key considerations for the benefit-risk assessment of viral vector vaccines. This will facilitate key stakeholders to anticipate potential safety issues and interpret or assess safety data. This would also help improve communication and public acceptance of licensed viral vector vaccines.


id: cord-354818-yf5lvbs1
author: von Linstow, Marie-Louise
date: 2020-08-13
url: https://doi.org/10.1016/j.vaccine.2020.08.010
doi: 10.1016/j.vaccine.2020.08.010
title:
  Self-reported immunity and opinions on vaccination of hospital personnel among paediatric healthcare workers in Denmark

abstract:
  BACKGROUND: Denmark has no general recommendations for vaccination of healthcare workers (HCWs). We explored the self-reported immunity to varicella, measles, mumps, and rubella, reasons for receiving the influenza vaccine or not, and opinions on vaccination of HCWs against varicella, MMR, pertussis, diphtheria, and influenza among staff from departments with a high risk of exposure to infectious agents. METHODS: From May 2019 to August 2019, a structured questionnaire was distributed to clinical and non-clinical HCWs at a tertiary and a general paediatric department in Denmark. Self-reported immunity was defined as either previous infection or vaccination against the disease. RESULTS: Of 619 employed HCWs, 555 (90%) were included. A large proportion were unsure of or denied previous vaccination or infection with measles (20.1%), mumps (30.2%), rubella (21.4%), varicella (12.1%), pertussis (44.1%), and diphtheria (32.1%). Non-clinical personnel and employees born in 1974–1983 had the lowest level of self-reported immunity. Mandatory vaccination of non-immune HCWs was approved by 54–68.9% of participants, and any kind of vaccination (mandatory or as an offer at hospitals) was approved of up to 95.3% of all participants depending on the disease. During the season 2018/19, 214 (38.6%) HCWs received the influenza vaccine, including 20.3% of non-clinical staff, 34.8% of nurses and 56.5% of doctors (P < 0.001). Reasons for lack of vaccine uptake were mainly employees considering themselves rarely sick, the vaccine was not regarded as necessary, forgetfulness or lack of time. Only 37.8% was in favour of mandatory influenza vaccination. CONCLUSIONS: A large proportion of paediatric HCWs were not aware of their immune status against important vaccine-preventable diseases. >90% supported vaccination of HCWs, with two out of three supporting mandatory MMR, pertussis and diphtheria vaccination. Better information and an official immunisation policy of non-immune HCWs in Denmark is warranted.


