cord-000050-tfcerilc	2008	
cord-000194-cwzpb8fu	2007	To test the hypothesis that whole-virion would be more immunogenic than conventional split-virion or subunit vaccines and may be adaptable to the antigen-sparing strategy, an inactivated, monovalent infl uenza A (H5N1), whole-virion vaccine was prepared from a highly virulent strain A/Vietnam/1194/2004 strain by removing the polybasic amino acids at the cleavage site, making the virus no longer pathogenic. Vaccination of mice with a live attenuated infl uenza vaccine or an alum-adjuvanted inactivated infl u-enza vaccine based on a related H5 HA from a nonpathogenic avian infl uenza virus, A/Duck/Pottsdam/1042-6/86 (H5N2), limited the disease severity and reduced deaths following challenge with a current highly pathogenic infl uenza (H5N1) (23) . Genes of highly conserved proteins such as the nucleoprotein or M2 proteins could be included in adenovirus vector-based vaccines because immune responses against these infl uenza viral antigens provide protection in animal models (24, 25) . Cross-protective immunity in mice induced by live-attenuated or inactivated vaccines against highly pathogenic infl uenza A (H5N1) viruses
cord-000262-4owsb0bg	2010	In settings like Hong Kong, with the infrastructure and resources to implement such measures and N Decisions regarding pandemic response during the exigencies of a public health emergency must be judged according to the best evidence available at the time. Reduce and delay community spread somewhat at the earliest stage to allow better preparation for mitigation response [15] Completely prevent entry of infected individuals due to suboptimal sensitivity and asymptomatic (including infected and within incubation period) or subclinical presentation [16] Many countries did not attempt these measures because of logistics, stage of pandemic [22] or other cost-benefit considerations [16] China Hong Kong SAR Japan Personal protective measures (e.g., face masks, hand hygiene, cough etiquette, early self-isolation when ill) Reduce risk of infection to self and close contacts (if self is ill and infected) [27, 28] Have not been evaluated whether they can provide significant populationlevel protection
cord-000452-1gd006zy	2011	
cord-001260-6krujv2m	2014	To thoroughly assess vaccine efficacy, full dose–response curves were generated for heroin-induced analgesia in both hot plate and tail immersion tests. In the research we disclose herein, both injection route and TLR9 agonist CpG ODN 1826 significantly affected antibody titer levels and opiate affinity, translating to marked differences in mitigation of heroin-induced analgesia. Mice were immunized with our first generation heroin vaccine (heroin− KLH conjugate formulated with alum adjuvant), and antibody titers were measured by ELISA against heroin−BSA conjugate. The current study highlights the impact of varying the injection route of our first generation heroin vaccine, along with enhancing immunogenicity by addition of the CpG ODN adjuvant. We have shown that the enhanced antidrug titers and opioid affinities from CpG ODN translate directly to reduced pharmacodynamics of the drug; in our case heroin-induced latency to nociception (analgesia) was greatly diminished in hot plate and tail immersion tests.
cord-002282-ldfa616a	2016	Another important advantage as emerging vaccine is the more effective activation of key aspects of the immune response to achieve potent immune stimulation and to provide immunological memory for long-lasting protection [22, 23] Plant-based platforms including whole plant, organs or cell and expression technology to produce target antigens of interest are diverse [38] [39] [40] . In the case of plant-derived HBV vaccines, the first report was on the expression of the small hepatitis B surface antigen (S-HBsAg) in transgenic tobacco plants. In the transgenic tobacco plant transformed with the S-HBsAg gene controlled by the 35S promoter, expression levels were very low: less than 0.01% total soluble protein and less than 10 ng/g fresh weight in leaf tissues. Expression of the human hepatitis B virus large surface antigen gene in transgenic tomato plants Oral immunization of human with transgenic lettuce expressing hepatitis B surface antigen
cord-002333-90f9vr0a	2016	The coprimary immunogenicity objective determined whether adjuvanted vaccines elicited an immune response against the vaccine-homologous virus, 21 days after the second vaccine dose per US and European licensure criteria in the per-protocol cohort (n = 389). The coprimary immunogenicity objective was to evaluate whether the adjuvanted A/Shanghai/2/2013 (H7N9) vaccines elicited an immune response against the vaccine-homologous virus that met US CBER and European Committee for Medicinal Products for Human Use (CHMP) immunogenicity targets at day 42 (21 days after the second vaccine dose). In a sub-analysis of the homologous immune response by age, the adjuvanted vaccine was immunogenic in both age groups, with SPRs ≥80.0% in participants 41-64 years of age, despite lower GMTs (Table 3 ). The results of this phase I/II randomized, placebo-controlled trial showed that 2 doses of the H7N9 AS03-adjuvanted vaccine elicited a robust immune response in healthy adults up to 64 years of age, with an acceptable safety profile.
cord-002500-9p2n8tjx	2017	The other vaccine modality being assessed as an Ebola vaccine candidate is the recombinant vesicular stomatitis virus encoding EBOV glycoprotein (rVSV-ZEBOV), which is an attenuated replication-competent viral vector. In the absence of any gold standard for measuring humoral immunity against Ebola virus, a wide variety of assays were used to evaluate antibody responses to vaccines during the recent EVD outbreak. Many of the other binding assays used in these Phase I trials correlate strongly and, in particular, it is useful that the standardized glycoprotein ELISA and pseudotyped lentivirus assays each correlate strongly with neutralizing titres against live Ebola virus as these assays avoid the need to work at high containment levels, but may be used to indicate the presence of antibodies with neutralizing activity. In a pre-clinical NHP model, IgG responses after immunization with AdHu5-based Ebola virus vaccines were measured using an ELISA against GP, where 100% protection against a lethal challenge was predicted by titres of 3700 or greater, while a titre of around 2000 predicted 85% survival.
cord-002842-4evbeijx	2018	title: Novel Immunoinformatics Approaches to Design Multi-epitope Subunit Vaccine for Malaria by Investigating Anopheles Salivary Protein This study represents a series of immunoinformatics approaches to design multi-epitope subunit vaccine using Anopheles mosquito salivary proteins. Finally, molecular docking and simulation study was performed for the vaccine protein and TLR-4 receptor, to determine the binding free energy and complex stability. Therefore, in this study, we applied a novel immunoinformatics approach to design multi-epitope based subunit vaccine that may prevent the disease by maintaining the host hemostasis by the inhibition of anticoagulant and anti-inflammatory proteins present in mosquito saliva. Predicted CTL epitopes for each salivary protein was used as an input sequence and the result was obtained in the form of the score, where higher score determines that greater will be the probability of eliciting an immune response.
cord-003403-ypefqm71	2018	When initial Zika vaccine clinical trials were being designed and launched in response to the outbreak, there were no standardized sets of viral and immunological assays, and no approved diagnostic tests for Zika virus infection. In an outbreak situation, such as with Zika, it is important to have the ability to quickly develop both diagnostic kits for public health purposes and vaccine clinical assays to support pre-clinical studies and early stage clinical trials. Additionally, cross-reactivity in a number of immunological assays and the short time frame in which viremia can be detected in bodily fluids necessitated the institution of an algorithm to confirm ZIKV infection that was based on a combination of risk factors, clinical symptoms and diagnostic test results [71] . Rapid response to an emerging infectious disease-lessons learned from development of a synthetic DNA vaccine targeting Zika virus
cord-003567-h8uq5z8b	2019	
cord-003656-7mzsaz7a	2019	
cord-003764-141u6ax7	2019	
cord-003806-ctass7hz	2019	
cord-003828-bhfghcby	2019	
cord-003926-ycdaw2vh	2019	Of note, the first demonstration of immunoprotection was as part of a 1953 study to define the ultrastructural characteristics of Zika virus, that found intramuscular vaccination of mice with infectious viral filtrates protected against cerebral infection [36] . In pre-clinical studies, vaccinated mice and non-human primates were shown to develop B and T-cell immune responses against the Zika virus envelope and protected against development of neurologic disease and death in immunosuppressed, interferon α, β receptor deficient (IFNAR) mice [43] . A subsequent study in non-human primates vaccinated twice at four-week intervals with alum generated binding and microneutralization antibody titers of 3.54 and 3.55 log10, respectively, and complete protection against viremia and viruria following challenge with either Brazilian or Puerto Rican strains of Zika virus [47] . Guillain-Barre Syndrome outbreak associated with Zika virus infection in French Polynesia: A case-control study
cord-004078-d1pd09zj	2020	The majority of the licensed carbohydrate-based vaccines such as Streptococcus pneumonia, Neisseria meningitides, Haemophilus influenzae type b and Salmonella typhi Vi belongs to this category in which the carbohydrate antigens were isolated form microbial cultures and further conjugated to the carrier protein [32] . Many attempts to develop a monovalent MenB conjugate vaccine failed because the structural similarity between the capsular polysaccharides (comprised of α-2,8linked sialic acid) of MenB and components of the human neuraonal cells caused autoimmune issues in clinical tests. In short, the unimolecular pentavalent vaccines that combined several carbohydrate antigens and carrier protein conjugates could simulate immune response against the heterogeneous carbohydrate epitopes expressed on the surface of cancer cells. To overcome the shortage of MOE, many studies focus on modification of TACAs vaccines, which not only could generate stronger immunogenicity but also induce cross-reactive antibodies recognizing native carbohydrate antigens on the tumor cells.
cord-004181-exbs3tz7	2020	The efficacy of the chimeric multiepitope construct as a recombinant protein vaccine and DNA vaccine was evaluated in Nile tilapia, followed by S. The epitopes of immunogenic proteins were predicted by the BCPREDS server based on B cell epitopes to be used in chimeric multiepitope vaccine construction. In this study, not only immunogenic proteins from the immunoproteomics analysis were used but also other subunit vaccine candidates were subjected to epitope prediction and combined to produce a chimeric multiepitope vaccine. The recombinant chimeric multiepitope protein vaccination showed that 45F2 and 42E2 produced cumulative mortality rates of 30.00 ± 10.00% and 26.67 ± 5.77%, respectively, which were significantly lower than those of the negative control group, at 70% (P < 0.05) (Fig. 6A) . agalactiae serotype Ia and III demonstrated that fish vaccinated with recombinant protein vaccine 42E2 and 45F2 showed cross-reactivity to whole cell lysate of S.
cord-004274-cot05vx7	2020	"STATE-OF-THE-ART" mRNA CONSTRUCTS AND DELIVERY TECHNOLOGIES The core principle behind mRNA as a technology for vaccination is to deliver the transcript of interest, encoding one or more immunogen(s), into the host cell cytoplasm where expression generates translated protein(s) to be within the membrane, secreted or intracellularly located. Perspective #2: Translational sciences will inform preclinical and clinical studies to promote rapid downselection of constructs and formulations A key aspect of vaccine development efforts is the goal of making early informed decisions, based on objective data that favor or disfavor a particular candidate. 64 The current focus from a clinical perspective is to optimize the benefit (immunogenicity and efficacy) while reducing the risk (safety) profile of a candidate mRNA vaccine by optimizing the quality attributes that dictate expression and/or augmenting delivery. Thus, early-phase clinical trials need to be designed in a way to appropriately capture the inflammatory component intrinsic to all mRNA vaccines, given that several intracellular innate immune response sensors are activated by RNA.
cord-004348-4jdn4kw6	2020	In a preclinical study, ferrets sequentially immunized with heterologous influenza strains including live attenuated influenza vaccine (LAIV) bearing an H8 head domain and an H1 stem domain (cH8/1) and a split-inactivated vaccine bearing an H5 head domain and an H1 stem domain (cH5/1), conferred superior protection against challenge with pandemic H1N1 virus following different prime-boost combinations and immunization regimens [49] . Flu-v has been shown to induce a specific CD8 + response against these conserved epitopes and confer protection against heterotypic infection in mice [59] , and a Phase Ib challenge trial also showed that the blood cells from immunized subjects exhibited cross reactive immunity against different influenza viruses [62, 63] . Endoglycosidase H is added after harvest to trim high mannose residues down to a single GlcNAc. The resultant monoglycosylated split vaccine provides a more diverse immune response and more effective cross-strain protection than conventional egg-based vaccines.
cord-004435-l66ost6q	2020	
cord-004518-jd1wxobz	2007	Immunization with plasmid DNA (DNA-based vaccination) is a relatively novel technique for the efficacious stimulation of a specific cellular and humoral immune response to protein antigens. The application of DNA vaccine to the liver is associated with enormous protein expression followed by a strong antibody-and cell-mediated immune response. One highly efficacious delivery system for DNA vaccines, or, more precisely, genetic vaccines, is based on recombinant viral vectors derived either from attenuated viruses used for preventive vaccination (vaccinia, poliovirus, hepatitis B virus, measles virus) or from viruses such as human adenovirus (HAdV), adeno-associated virus (AAV), alphavirus, vesicular stomatitis virus (VSV), or poxviruses other than vaccinia [41] . In animal experiments a recombinant measles vector expressing HIV-1 envelope antigen induced neutralizing antibodies and envelope-specific CD4 + and CD8 + cell responses after a single dose [67] . Although some mucosal response is detectable after a systemic DNA vaccination, i.m. injection and gene-gun delivery of plasmid DNA have a limited ability to induce mucosal immune responses [99] .
cord-005081-kxrzv16n	2010	We are using the following approaches to the development of industrial production: use of nanoparticles and nanoemulsions as functional adjuvants, construction of totally-safe strains for live attenuated influenza vaccines with deletions of molecular determinants of pathogenicity, application of protein and chemical chaperones to provide self-assembly of haemagglutinin molecules of the H1N1v-2009 virus, and impregnation of whole-virion preparations with nanoparticles to enhance antigenicity. Europe and the United States agreed to allot grants and worked out programs for developing novel technologies and vaccine preparations with improved qualities: a new generation of LAIV, that is, delNS1 vaccines with a limited replicative potential, LAIV with deletions of pathogenicity factors in genes, latest variations of subunit vaccines enhanced by adju vants, and capsid nanovaccines and nanovaccines based on inactivated viruses and virus like particles [14] . A marked breakthrough in the construction of recombinant vaccines is related to the use of insect cells and the obtaining of virus like particles (VLPs) based on baculovirus expression vectors.
cord-005246-cskb0njm	1993	
cord-005400-50lmj4op	2005	Of the 80-plus known infectious agents pathogenic for humans, there are now more than 30 vaccines against 26 mainly viral and bacterial infections and these greatly minimize subsequent disease and prevent death after exposure to those agents. Vaccines are designed as a prophylactic measure to induce a lasting immune response so that on subsequent exposure to the particular infectious agent, the extent of infection is reduced to such an extent that disease does not occur (1). More recently, the use of avipox viruses such as fowlpox and canarypox, which undergo an abortive infection in humans, is being used in humans as vectors of DNA coding for antigens of other infectious agents for which vaccines are not yet available (2). Live, attenuated agent vaccines have the potential to stimulate strong humoral and cell-mediated immune responses that can be highly effective in preventing or clearing a later infection in most recipients.
cord-006252-cbelsymu	2012	
cord-006890-81wv1s33	2014	
cord-006892-n2ncamqh	2018	
cord-007440-7gcpk9x9	2005	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 ).
cord-007681-vhghhvnu	2009	Factors contributing to the decision to reassess the recommendations included a shift in national pandemic planning assumptions to a more severe pandemic scenario extrapolated from the 1918 pandemic (Table 1 ); recognition that the HHS guidance did not include groups that could be considered for prioritization such as border protection personnel or the military; a broader understanding of the risk to essential services stimulated by the NIAC report; and a series of public engagement meetings convened by the CDC, where participants identified protecting essential community services as the most important goal for pandemic vaccination rather than protecting those who are at highest risk (Public Engagement Pilot Project on Pandemic Influenza 2005). Reflecting the similar value placed by the public on protecting persons who provide pandemic healthcare, who maintain essential community services or are at high occupational risk, and protecting children, each of the highest vaccination tiers for a severe pandemic includes groups from each category (Table 4) .
cord-007710-0u5ot5h4	2013	Several technological and conceptual advances have recently occurred that make RSV vaccine development more feasible, and this collected knowledge is intended to help inform and organize the future contributions of funding agencies, scientists, regulatory agencies, and policy makers that will be needed to achieve the goal of a safe, effective, and accessible vaccine to prevent RSV-associated disease. Barik, this volume), and suggest that vaccines that elicit responses that block or avoid the immunomodulation associated with wild-type RSV infection without enhancing disease could provide more potent and durable immunity than natural infection. These include the need for improved animal models, better understanding of mucosal immunity, more definitive clinical endpoints to use in efficacy trials, alternate vaccination strategies to protect the young infant (e.g., vaccinating pregnant women) and other high risk populations for whom vaccination may have limited effectiveness, and remedies for liability concerns.
cord-007733-zh8e76w7	2009	The efficacy of seasonal vaccines is linked to their ability to induce virus-neutralizing antibodies, which provide subtype-specific protection against influenza A viruses. Alternatively, the scientific community could step up efforts to generate a universal vaccine against influenza A viruses that provides broadly cross-reactive protection through the induction of antibodies or T cells to conserved regions of the virus. Alternatively, the scientific community could step up efforts to generate a universal vaccine against influenza A viruses that provides broadly cross-reactive protection through the induction of antibodies or T cells to conserved regions of the virus. WHO recommends three measures to lessen the impact of the next influenza virus pandemic: (1) increased surveillance to allow for the earliest possible warning that a human pandemic has started; (2) early intervention to stall global spread and prevent further adaptations; and (3) development of an effective pandemic vaccine.
cord-008716-38sqkh9m	2001	
cord-008881-579ronfq	1981	title: MULTISITE INTRADERMAL ANTIRABIES VACCINATION: Immune Responses in Man and Protection of Rabbits Against Death from Street Virus by Postexposure Administration of Human Diploid-Cell-Strain Rabies Vaccine Lymphocyte transformation, production of neutralising antibody, and the development of antirabies IgG antibody were studied in ten healthy volunteers in response to 0·8 ml of human diploid-cell strain (HDCS) rabies vaccine administered on one occasion in divided doses in 8 intradermal (i.d.) sites. Lymphocyte transformation, production of neutralising antibody, and the development of antirabies IgG antibody were studied in ten healthy volunteers in response to 0&middot;8 ml of human diploid-cell strain (HDCS) rabies vaccine administered on one occasion in divided doses in 8 intradermal (i.d.) sites. This resounding success has been repeated in trials in Germany and the U.S.A. using 5 or 6 doses of human diploid-cell strain (HDCS) rabies vaccine and human rabies immune globulin.'', Thus, almost a century after the post exposure treatment of man began, effective antirabies prophylaxis appears to have been achieved.
cord-009381-q9s38fkh	2007	The federal government regulations for the United States of America regarding veterinary vaccines 9 Contamination with extraneous agents 9 Failure to inactivate agent in killed vaccine 9 Residual virulence of vaccine organisms 9 Vaccination of immunosuppressed animal 9 Immune suppression induced by the vaccine 9 Excessive induction of cytokine release 9 Multiple vaccines administered concurrently 9 Hypersensitivity to vaccine antigens Type I--immediate type Type IImcytotoxic type Type IIImimmune complex type Type IVmdelayed type 9 Triggering or exacerbation of hypersensitivity to nonvaccine antigens Allergies Autoimmune disease 9 Induction of neoplastic changes 9 MLV BVD vaccine triggering mucosal disease in persistently infected cattle are found in the Virus Serum Toxin Act (VSTA) in Title 9 of the Code of Federal Regulations (9 CFR). An example of vaccine-induced disease resulting from administration of vaccine to unhealthy animals is the induction of encephalitis by MLV canine distemper virus vaccine in dogs infected with canine parvovirus (Krakowka et al., 1982) .
cord-009383-ozx5u0t3	2007	
cord-009947-0zz4x8li	2007	
cord-010266-elhgew3x	1998	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.
cord-011325-r42hzazp	2019	Even if only based on a temporal sequence of events, it is important that such safety concerns are rapidly investigated with robust epidemiological studies to allow mitigation procedures to be put in place if an association is confirmed or, if unfounded, to have the necessary evidence to sustain public confidence in the vaccination programme without which coverage drops and disease control is lost. The self-controlled case-series method (SCCS) was designed for rapid unbiased assessment in vaccine safety studies using available disease surveillance data that may not be amenable to cohort analysis. As with all vaccine safety studies, but particularly in the case of narcolepsy and Pandemrix™ where the association was completely unexpected, the key to demonstrating causality was consistency of results from well-designed studies in different settings. Risk of narcolepsy after AS03 adjuvanted pandemic A/ H1N1 2009 influenza vaccine in adults: a case-coverage study in England
cord-011370-as2v2c2h	2019	
cord-011486-5osu6hdu	2020	title: Rotavirus infection in children in Southeast Asia 2008–2018: disease burden, genotype distribution, seasonality, and vaccination Here we summarize the virology, disease burden, prevalence, distribution of genotypes and seasonality of RVs, and the current status of RV vaccination in Southeast Asia (Cambodia, Indonesia, Lao People''s Democratic Republic, Malaysia, Myanmar, Philippines, Singapore, Thailand, and Vietnam) from 2008 to 2018. Rotavirus vaccine is highly cost effective in Southeast Asian countries because the ratio between cost per disability-adjusted life years (DALY) averted and gross domestic product (GDP) per capita is less than one. The prevalence of diarrheal diseases in Southeast Asia countries varies, but the mortality trend associated with diarrhea and especially RV infection has been decreasing in recent years. We collected RV surveillance data from 9 countries in Southeast Asia (Cambodia, Indonesia, Lao PDR, Malaysia, Myanmar, Philippines, Singapore, Thailand, and Vietnam) for the years 2008-2018 to estimate the proportion of RV gastroenteritis (RVGE) ( Table 2) .
cord-013290-j3assowx	2020	
cord-013326-qsqaimsy	2020	
cord-014462-11ggaqf1	2011	Molecular diagnosis based on reverse transcription (RT)-PCR s.a. one step or nested PCR, nucleic acid sequence based amplification (NASBA), or real time RT-PCR, has gradually replaced the virus isolation method as the new standard for the detection of dengue virus in acute phase serum samples. Non-genetic methods of management of these diseases include quarantine measures, eradication of infected plants and weed hosts, crop rotation, use of certified virus-free seed or planting stock and use of pesticides to control insect vector populations implicated in transmission of viruses. The results of this study indicate that NS1 antigen based ELISA test can be an useful tool to detect the dengue virus infection in patients during the early acute phase of disease since appearance of IgM antibodies usually occur after fifth day of the infection. The studies showed high level of expression in case of constructed vector as compared to infected virus for the specific protein.
cord-014901-d9szap94	2015	
cord-016126-i7z0tdrk	2018	The present book chapter is intended to explore the potential of RV approach to select the probable vaccine candidates against coronavirus and validate the results using docking studies. Reverse vaccinology is based on same approach of computationally analysing the genome of pathogen and proceeds step by step to ultimately identify the highly antigenic, secreted proteins with high epitope densities. The most appropriate targets as vaccine candidates are those which possess the adhesion-like properties because they not only mediate the adhesion of pathogen''s proteins with cells of host but also facilitate transmission of virus. None of the 11 proteins of MERS-CoV possessed any clue of allergenicity as per prediction results from AlgPred and Allertop tools; it means that no vigorous immune responses will be mounted if the epitopes from these proteins will be adopted as vaccine candidates. Identification of potential antigens from non-classically secreted proteins and designing novel multitope peptide vaccine candidate against Brucella melitensis through reverse vaccinology and immunoinformatics approach
cord-016178-2ix6c0he	2014	These efforts towards the expression of the S-antigen of TGEV in maize seed, its effectiveness at inducing neutralizing antibody production in the colostrum of gilts, and its efficacy in protecting piglets against challenge by virulent TGEV are summarized here. Potentially, the methods to protect naïve piglets at highest risk from TGEV infection are to provide immune colostrum by vaccinating sows and an oral/nasal vaccine to boost secretory neutralizing antibody levels. The induction of neutralizing antibodies in both serum and colostrum was examined in gilts following the administration of oral TGEV vaccine in maize comprising a subunit vaccine of the S-protein expressed in corn (Lamphear et al. Administration of antigen over a 4-day period gave the highest levels of protection against live challengeeven higher than oral vaccination with a modified live virus (Fig. 8.4 ; see Sect. Protection with a subunit antigen expressed in corn, exclusively by the oral route, is shown for the first time to be effective in piglets, the target species for immunization.
cord-016200-zfh20im0	2013	In 1998 a new era was opened in vaccine delivery when researchers supported by the National Institute of allergy and infectious diseases (NIAID) have shown for the first time that an edible vaccine can safely generate significant immune responses in people. Transgenic tobacco is successfully engineered for the production of edible vaccines against hepatitis B antigen using ''s'' gene of hepatitis B virus (HBV). Egyptian scientists have genetically engineered the maize plants to produce a protein known as HbsAg which elicits an immune response against the hepatitis B virus and could be used as a vaccine. It has been studied that genes are successfully expressed in experimental model plants and when given orally to animals, the extract of transgenic plant containing the antigen induced serum antibodies, thus can be used to produce the edible vaccine.
cord-016222-dltsdqcm	2016	
cord-016268-xcx1c0da	2013	Factors in favor of plant systems as sources of animal derived proteins include: the potential for large-scale, low-cost biomass production using agriculture; the low risk of product contamination by mammalian viruses, blood borne pathogens, oncogenes and bacterial toxins; the capacity of plant cells to correctly fold and assemble multimeric proteins; low downstream processing requirements for proteins administered orally in plant food or feed; the ability to introduce new or multiple transgenes by sexual crossing of plants; and the avoidance of ethical problems associated with transgenic animals and the use of animal materials (Doran 2000 ) . In parallel with evaluation of plant-derived Hepatitis B surface antigen, Mason and Arntzen explored plant expression of other vaccine candidates including the labile toxin B subunit (LT-B) of entertotoxigenic Escherichia coli (ETEC) and the capsid protein of Norwalk virus (NVCP).
cord-016371-zkawdcac	2013	
cord-016475-7ldxvbpz	2006	After influenza virus infection antibodies directed against all major viral proteins can be detected in humans and the level of serum antibodies correlate with resistance to disease (Couch, 2003; Couch and Kasel, 1983; Coulter et al., 2003; Nichol et al., 1998; Potter and Oxford, 1979) . Nevertheless, IKK and NFκB might not only have anti-viral functions as two recent studies demonstrate that influenza viruses replicate much better in cells where NFκB is pre-activated (Nimmerjahn et al., 2004; Wurzer et al., 2004) . Apoptosis is mainly regarded to be a host cell defense against virus viruses (reviewed in: Julkunen et al., 2000; Ludwig et al., 2003; infections since many viruses express anti-apoptotic proteins to prevent this cellular response. Influenza virus-induced NF-kappaB-dependent gene expression is mediated by overexpression of viral proteins and involves oxidative radicals and activation of IkappaB kinase
cord-016508-39glgeft	2019	Innovative preventive vaccines against emerging and neglected infectious diseases, such as Zika, dengue, chikungunya, influenza, and HIV/AIDS, are examined here from bioeconomics and global sustainability perspectives, aiming to integrate public health and biotechnology market approaches. This scenario of increasing global demand for vaccines in the next decade is supported by epidemiological indicators: annual burden of new HPV-related cancers worldwide to the tune of 670,000; rise of Zika into a public health emergency with over 86 countries reporting 230,000 cumulative confirmed cases of infection between 2015 and 2018; very high prevalence of HSV which infects approximately 67% of the world population under 50 years of age; continued prevalence of tuberculosis which infects 10 million and takes 1.5 million lives each year despite the progress made toward eliminating the disease; and rise in HIV infections worldwide over 36.9 million (WHO 2018; Global Industry Analysts 2018).
cord-016594-lj0us1dq	2012	In the wider context of the experimental discovery of vaccine antigens, with particular reference to reverse vaccinology, this chapter adumbrates the principal computational approaches currently deployed in the hunt for novel antigens: genome-level prediction of antigens, antigen identification through the use of protein sequence alignment-based approaches, antigen detection through the use of subcellular location prediction, and the use of alignment-independent approaches to antigen discovery. When looking at a reverse vaccinology process, the discovery of candidate subunit vaccines begins with a microbial genome, perhaps newly sequence, progresses through an extensive computational stage, ultimately to deliver a shortlist of antigens which can be validated through subsequent laboratory examination. Conventional empirical, experimental, laboratory-based microbiological ways to identify putative candidate antigens require cultivation of target pathogenic micro-organisms, followed by teasing out their component proteins, analysis in a series of in-vitro and in-vivo assays, animal models and with the ultimate objective of isolating one or two proteins displaying protective immunity.
cord-016713-pw4f8asc	2013	The use of nonviral particulate carriers for DNA-based vaccination could provide better and safe delivery of encapsulated genetic material, circumvent the need for muscle involvement and facilitate instead the uptake of the Fig. 4 Schematic representation of immunological response greeted by novel DNA-loaded nanocarrier DNA by APCs. However, transfection of APCs with encapsulated DNA into particulate carrier systems will be dependent upon choice of carrier surface charge, size, and lipid/polymer composition, or presence of other biological [e.g., interleukin 2 and interferon-γ (IFN-γ)]. Modification of lipid/DNA complexes by the polymer poly(D,L-lactic acid) was found to be consistently and significantly more effective than either unmodified liposomal DNA or naked DNA in eliciting transgene-specific immune responses to plasmid-encoded antigen when administered by the s.c. route (Bramwell et al.
cord-016903-z2vqfq98	2007	
cord-017291-bhe34dky	2017	Children aged <5 years (especially those <2 years) and those with underlying illness such as cardiac, respiratory and severe neurologic disease have an increased risk of severe outcomes associated with influenza. Vaccine cannot be given to children aged <6 months but maternal influenza immunization during pregnancy is recommended and can confer protection to the young infant. The highest rates of influenza-associated hospitalizations and deaths are typically seen in individuals aged ≥65 years, <5 years and those with underlying medical conditions that confer an increased risk for severe influenza [9] . Therefore, in Table 2 .1 Children at high risk of severe influenza in whom influenza antiviral treatment is recommended by the Centers for Disease Control and Prevention (CDC) and American Academy of Pediatrics (AAP) current guidance [9, 39] 1.
cord-017838-fbotc479	2010	
cord-017841-57rm046y	2012	What the pharmaceutical industry needs is the capacity to apply the same systematic, automated, high-technology approaches used to identify new small-molecule drugs to the discovery and development of vaccines. Just over a decade ago, Rino Rappuoli used the expression "reverse vaccinology" to describe development of vaccines using a genomic-based approach, rather than the ponderous empirical methods favoured then, and still in use today. This book looks in turn at reverse vaccinology and the identification of putative candidate antigens, at the discovery of a wide range of different types of adjuvants, and finally at the development of sophisticated new delivery mechanisms, such as liposomes and other applications of nanotechnology. They also highlight how advances in genome-based techniques and in so-called next-generation sequencing approaches and technologies will help to enhance reverse vaccinology, enabling timely identification of novel candidate antigens for new, emerging, or recrudescent infectious diseases.
cord-018018-2yyv8vuy	2018	1995) was also used to demonstrate the efficacy of two very different plant-made papillomavirus vaccines, a few years after the demonstration that Human papillomavirus L1 major capsid protein virus-like particles could be produced in transgenic tobacco or potato (Biemelt et al. The early historical account of molecular farming for veterinary vaccines given above gives an idea of the array of technologies available and used up to the mid-2000s: transgenic and transplastomic expression of subunit proteins; recombinant plant viruses either used to express whole vaccine candidate genes, or to display chosen peptides fused to their capsid proteins; fusion of vaccine protein genes to carrier proteins to improve immunogenicity, including by inherent adjuvant properties; candidate parenteral and oral vaccines to both viruses and bacteria; therapeutics for animals made in plants; use of plant cell cultures to make antigens.
cord-018040-k0h5ejjt	2009	
cord-018165-afzjx2ci	2013	
cord-018265-twp33bb6	2007	A live vaccine based on a master virus strain developed at the Institute of Applied Microbiology (Austria) by growing wild influenza virus in Vero cells at 25°C was also demonstrated to be safe, well-tolerated and immunogenic after intranasal immunization in young adults [18]. Candidate vaccines should be able to replicate and induce a protective immune response in young infants, even in the presence of maternally acquired antibodies. This demonstrates that antibodies play a major role in protection against this disease, whereas T-cell immunity targeted to internal viral proteins appears to contribute to clearance. The second generation of PS-based conjugate vaccines stimulates stronger antibody responses, even in infants, young children and immune deficient individuals, as well as immunological memory. The resulting proteins are then used to perform immunological and/or functional studies to select the most promising candidates (e.g., able to induce the production of microbicidal or neutralizing antibodies, capacity to confer protective immunity).
cord-018497-oy7hsrpt	2005	
cord-018677-gmitz3gg	2005	In these studies volunteers are typically allocated at random to receive the vaccine or a comparison agent, usually a placebo, and are then challenged at a defined interval after vaccination with an inoculum of the pathogen predicted to cause the target disease in nearly 100% of the control group. Phase III studies are designed as randomized, controlled trials with clear hypotheses, and are conducted in the target group for whom vaccine licensure is desired and in a population that normally experiences the target infection. Definition of immunological correlates of vaccine protection is very important because such correlates permit assessments of the protection of the tested vaccine and ones suitably similar to it in small, short-term studies with immunological endpoints, without resort to full-scale, Phase III efficacy trials with clinical infection endpoints. The successive phases of clinical evaluation of vaccine candidates allow for acquisition of critical information about vaccine safety, immunogenicity, excretion, transmission, and protection in an incremental fashion, while minimizing the risks to subjects who volunteer to participate in these studies.
cord-018811-zhwr3h07	2010	The international investment into public health measures for a global human outbreak of avian H5N1 influenza together with a focus of swine influenza H1N1 is leading to enhanced production of conventional vaccine and to a new research searchlight on T-cell epitope vaccines, viral live-attenuated carriers of influenza proteins, and even more innovative substrates to cultivate virus, including plant cells. This was particularly well demonstrated by studies during the swine influenza campaign in the USA in 1976, when many observers reported results, which ultimately led to the recommended use in children of two doses of split-type rather than whole-virus vaccines. It has been known for many years that the serological response to inactivated vaccine depends on the previous experience of the recipient to infection by viruses of the same subtype of influenza A virus as that present in the vaccine. Comparison of inactivated vaccine A/HongKong/68 (H3N2) given intranasally or subcutaneously showed that following challenge with live virus only those who had developed a serum antibody response after vaccine by either route resisted infection.
cord-018969-0zrnfaad	2015	New vaccines and vaccination strategies are being developed including the use of attenuated live mycobacteria, recombinant microorganisms, and subunits, prime-boost strategies based on the successive administration of a certain mycobacterial antigen under two different vaccine vectors, and DNA vaccines [ 1 ] . However, several animal models have been developed to study the pathogenesis of Shigella , the resulting immune response against Shigella antigens, and the protection efficacy of candidate vaccines against shigellosis: [ 31 ] . The GAS M protein is the major protective antigen and an ideal target for vaccine development; however it contains heart tissue cross-reactive epitopes particularly in the conserved region [ 98 ] . Immunization of mice with a C-region peptide GAS vaccine candidate called J8 conjugated to the carrier protein diphtheria toxoid (dT) and co-delivery with an appropriate adjuvant led to protection against systemic and mucosal GAS infection [ 104 ] (Fig. 9.29 ).
cord-021637-f5wwn45z	2017	The vaccine industry is composed of companies that are engaged in any of the following activities: research (including that performed in industry and biotech), development, manufacture, or sales, marketing, and distribution of vaccines. In addition, new alliances will be formed between the big four manufacturers and emerging companies in India, China, and Brazil, to take advantage of increasing immunization rates in those countries as well as growth of their private markets. These product development partnership organizations (PDPs; essentially not-for-profit biotech companies) bring together specialized knowledge, animal models, immunologic assays, and field sites for vaccine testing as well as early capital investment to reduce the scientific technical risks, opportunity costs, and financial risk to their biotech and large pharma industrial partners.
cord-021937-p9vqpazu	2017	However, an increasing global integration is taking place, as multinational companies acquire Asian manufacturers (e.g., Sanofi-Aventis, France, acquired Shantha Biotechnics, India); Asian companies acquire or obtain technologies and distribution rights from European countries (e.g., inactivated polio vaccine by Serum Institute of India Ltd. acquiring Bilthoven Biologicals, Netherlands; Astellas, Japan, acquiring recombinant influenza hemagglutinin from Protein Sciences, U.S.; Thai Government Pharmaceutical Organization acquiring chimeric JE vaccine from Sanofi-Pasteur, France; and Biological Evans, India, acquiring JE vaccine from Intercell AG, Austria); and vaccine codevelopment is agreed between entities in developed and Asian countries (e.g., genetically modified, inactivated HIV vaccine codeveloped by Sumagen, Korea, and the University of Western Ontario, Canada; mycobacterial proteinAg85A candidate tuberculosis vaccine codeveloped by Tianjin CanSino Biotechnology, China, and McMaster University, Canada; universal influenza vaccine codeveloped by Xiamen Wantai and Sanofi-Pasteur, France; and novel pneumococcal conjugate vaccine codeveloped by SK Chemicals, Korea and Sanofi-Pasteur, France). The widely used first-generation inactivated suckling mouse brain (SMB)-derived vaccine is being replaced rapidly in economically disadvantaged countries by the Chinese developed and manufactured live attenuated or inactivated vaccine (SA14-14-2 strain) grown in primary baby hamster kidney (PHK) cells and in higher-income countries with Vero cell-derived inactivated vaccines (licensed in the United States, Australia, Canada, and Europe, as well as several Asian countries) or a replicating chimeric yellow fever-JE virus recombinant vaccine (manufactured in Thailand).
cord-021966-5m21bsrw	2009	
cord-022039-y0l943xg	2017	Section 901 of Title IX of the FDAAA authorizes the FDA to require certain postmarketing studies and clinical trials for prescription drug and biological products approved under the FDA should take action in response to such reports and whether the current pharmacovigilance plan is adequate. Critical information to be contained in the BLA include data derived from nonclinical laboratory and clinical studies that demonstrate that the manufactured product meets prescribed requirements for safety, purity, and potency. Following completion of IND studies demonstrating the safety and efficacy of the vaccine for a specific use and population the sponsor can submit a BLA to obtain a license for a new vaccine under section 351 of the PHS Act for commercial manufacture and distribution of the product.
cord-022168-qautse9a	2017	Specifically, the strategies that allow DNA vaccines to overcome antigenic diversity for viral infection and break immune tolerance for cancer therapy are explored. To overcome these obstacles, several approaches focusing on augmenting DNA uptake, maximizing protein expression, and enhancing antigen immunogenicity have been developed and tested in clinical trials. Therefore, one key element to improve DNA vaccine efficacy is to formulate a vaccine with an immunogenic cancer antigen so that it can prime T cells for immune responses. To date, the most successful and encouraging outcomes of using DNA vaccine in the clinical setting were obtained from treatment of malignant diseases where the etiological agent is of foreign viral origin, such as the human papillomavirus (HPV), as these viral agents can readily induce a strong immune response against cancerous cells harboring viral antigens.
cord-022349-z8w1wkm8	2007	
cord-023853-y5g4ceq9	2009	
cord-025366-haf542y0	2012	147, 148 In the United States, the CDC established the Clinical Immunization Safety Assessment (CISA) network in 2001 with the following primary goals: (1) to develop research protocols for clinical evaluation, diagnosis, and management of adverse events following immunization (AEFI); (2) to improve the understanding of AEFI at the individual level, including determining possible genetic and other risk factors for predisposed persons and high-risk subpopulations; (3) to develop evidence-based algorithms for vaccination of persons at risk of serious adverse events following immunization; and (4) to provide a resource of subject matter experts for clinical vaccine safety inquiries. Third, large population-based systems that link computerized vaccination data with health care encounter codes were used to conduct rapid ongoing analyses to evaluate possible associations of H1N1 vaccination with selected adverse events, including potential associations suggested by VAERS or other sources.
cord-027654-k0uby99n	2020	The advantages of their ability to induce cellular immunity, immunogenicity, safety, mode of antigen presentation, and other attractive features are countered by limitations in knowledge about clinical effi cacy, production methodologies, DNA vaccination as the initial vaccine constituent and replication-defective viral vectors, including modifi ed vaccinia Ankara virus (MVA), 21,28 rAd 22,23,27,29 or proteins to boost the initial response. 31, 32 In addition, the development of improved enhancer/ promoter regions can allow for even higher expression 5 and these vaccines have advanced into multiple human Phase I studies, alone or in combination with other gene-based vectors. Depending on their ability to target antigen presenting cells, ability to develop packaging lines, inherent immunogenicity of both the vector and insert, and other factors (Table 62 -2), these viral vectors are helping to improve vaccine effi cacy in a variety of infectious disease models. Comparative immunogenicity in rhesus monkeys of DNA plasmid, recombinant vaccinia virus, and replication-defective adenovirus vectors expressing a human immunodefi ciency virus type 1 gag gene
cord-032017-h0cj4izx	2020	Trying to "engage" families in order to educate and convince them of the wisdom of immunization is fine for the parents who want information and are willing to accept guidance, but this approach is clearly wasted on the entrenched vaccine deniers. But most Western families who fail to immunize their children know about vaccines and have ready access to physicians and nurses who could clearly explain their risks and benefits. It is time to stop the political correctness and "science speak." Parents should have the right to raise their children in accordance with their own preference, culture and religious beliefs, provided that their approach does not substantially increase the child''s odds of an avoidable illness or injury. Physicians must rise with one voice and say "enough!" By even considering the premise that vaccine denial can be a reasonable choice by a rational individual, we become enablers of child neglect.
cord-032600-lldbjm77	2020	2 Second-generation efforts employed more characterized materials, such as the biodegradable synthetic polymer poly (D,L-lactic-co-glycolic acid) (PLGA), which is a widely investigated nanoparticle adjuvant for controlled and effective delivery of vaccine antigens, including synthetic peptides. 32 Thus, pathogen-mimicking nanoparticles can be engineered to enhance the immune response by controlling when and where vaccine components are delivered intracellularly to APCs. 15 A plethora of particulate delivery systems for immunoengineering have been developed, which are summarized further in this review. Recently, we have combined such engineering and rational vaccine design approaches to develop a nanoparticle-based adjuvant and antigen-delivery system designed to be active in human newborns and infants. Furthermore, such formulations hold substantial potential for early life immunization by serving as a dual antigen/adjuvant delivery system that mimics the enhanced neonatal innate and adaptive immune responses elicited by the live Bacille Calmette-Guerin (BCG) vaccine.
cord-032751-pmclolvh	2020	Research Question 2: What are the SARS-CoV-2 vaccine behavioral intentions of adults in the U.S. when a health care provider recommends the vaccine? Importantly, because vaccine intent and/or need may be different for people who were previously infected with SARS-CoV-2 and perceived threat variables (discussed below) are usually only measured for future threats, only participants who answered "no" to the question "do you believe that you''ve had COVID-19" are included in the current study (n = 3,159). Step 3 of the hierarchical regression model, with all variables included, less education was associated with lower intent to receive a SARS-CoV-2 vaccine. The health belief variables that were significant in the full regression model were all positively associated with intent to receive a SARS-CoV-2 vaccine.
cord-035016-ipv8npdy	2020	Touted by many as a major tour de force, the ongoing ''race'' towards a vaccine is also exposing the intrinsic deficiencies of relying on for-profit pharmaceutical companies, that are governed by trade rules, financial speculation and market competition, to ensure the development of essential health technologies. This is antithetical to a collective intelligence effort that would allow scientists all over the world to creatively combine the best elements of our medical knowledge and technological advances into a diverse and innovative portfolio of vaccine candidates with the best chance to achieve our common public health goal (Torreele 2020b) . 5 A milestone resolution on transparency around medical R&D was passed at the 2019 World Health Assembly (Fletcher 2019 ), yet governments so far have failed to implement these commitments, despite huge financial investments in COVID-19 R&D that could have been used as leverage to demand transparency on scientific methods and data, as well as clinical trial costs, and set performance targets for the vaccines.
cord-163946-a4vtc7rp	2020	We approach this problem by proposing a novel pipeline VacSIM that dovetails Actor-Critic using Kronecker-Factored Trust Region (ACKTR) model into a Contextual Bandits approach for optimizing the distribution of COVID-19 vaccine. We evaluate this framework against a naive allocation approach of distributing vaccine proportional to the incidence of COVID-19 cases in five different States across India and demonstrate up to 100,000 additional lives potentially saved and a five-fold increase in the efficacy of limiting the spread over a period of 30 days through the VacSIM approach. In this paper, we introduce VacSIM, a novel feed-forward reinforcement learning approach for learning effective policy combined with near real-time optimization of vaccine distribution and demonstrate its potential benefit if applied to five States across India. Contextual Bandits play an action based on its current context, given a corresponding reward, hence are more relevant to real-world environments such as the vaccine distribution problem attacked in this work.
cord-252856-oc0zd11h	2016	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.
cord-254469-7q6xi2xx	2020	In March 2020, the first phase I clinical trial of a novel lipid nanoparticle (LNP)-encapsulated mRNA-based vaccine, mRNA-1273, which encodes the spike protein (S protein) of SARS-CoV-2, began in the United States (US). However, on March 16 2020, the first phase I clinical trial of a novel lipid nanoparticle (LNP)-encapsulated mRNA-based vaccine, mRNA-1273, which encodes the spike protein (S protein) of SARS-CoV-2, began in the United States (US), conducted by Moderna and the Vaccine Research Center (VRC) of the National Institute of Allergy and Infectious Diseases (NIAID) [12, 13] . Although mRNA vaccines are commencing human clinical trials, due to the rapid global spread of this new viral pandemic, it may not be possible to develop a safe and effective vaccine for SARS-CoV-2 in time to prevent the increasing number of deaths due to this novel RNA virus.
cord-254513-7d10vd86	2020	We show that trends in all of the measurements described above (modularity, global clustering coefficient, census and sizes of communities and echo 70 chambers) provide early warning signals of epidemic and vaccine crisis events for a coupled disease-behaviour model of childhood disease. (B.10) , we can see that lead distance decreases with strengthening social norm σ, with all the EWS eventually failing (giving negative lead distances, so that warnings follow K s -these are useless); modularity scores for the sub-networks formed by pro-vaccine � Q V � (Fig. B.10a ) and anti-vaccine � Q N � (Fig. B.10a ) agents give useful warnings for all social norms 340 σ ≤ 2.40625, while both the number of opinion changes � Θ * � (Fig. B.10b ) and the probability of having an infected neighbour SNHT �� Γ * �� give useful signals for σ ≤ 2.90625. In this paper, we tested the use and effectiveness of different network measures as early warning signals (EWS) of sudden transitions in the social and infection dynamics of a multiplex model of disease.
cord-254890-4ynsgu6c	2008	Live vaccine: Low passage lot for safety (GLP) on target species including pregnant animals in case indication is required High passage lot for efficacy: Onset of immunity and duration of immunity Inactivated vaccine: High passage lot for safety (GLP) and efficacy Licensing batches (10% commercial scale, GMP) -Consistency of production, process validation -Transfer of production process and control tests to manufacturing departments and quality control departments -Stability studies on antigen and final product in final container Field studies (GCP) -Safety -Efficacy derived from treated animals from which food is derived, and the consumer. The likely approach to develop vaccines would be, first, the cloning and site directed mutagenesis to turn the HA-gene into a non-pathogenic form, and, second, the production of so-called high growth re-assortants producing considerable amounts of the new HA protein, which is, among others, the protective antigen in influenza virus.
cord-255549-i2o6rs29	2017	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.
cord-255734-038xu4hq	2006	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
cord-257027-q2y7fewk	2011	Additionally, recent advances in immunogenetics and genomics should help in the understanding of the influence of genetic factors on the interindividual and interpopulation variations in immune responses to vaccines, and could be useful for developing new vaccine strategies. The publication of the Haemophilus influenzae genome, the first pathogen to have its complete genome sequence published as a result of an approach to genome analysis using new technologies of high-throughput sequencing (5) , has opened the mind of scientists to a range of new possible approaches to the study of microorganisms and has marked the beginning of a new era in vaccine development: the identification of pathogen candidate antigens based on the knowledge of the genome of the pathogen and on the understanding of microbial biology and host-pathogen interactions, an approach called reverse vaccinology (6) .
cord-257533-i85dyg8n	2020	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.
cord-257582-e9306xae	2020	The Vaccination Guidelines Group recognised numerous challenges in Latin America, for example: (1) lack of national oversight of the veterinary profession, (2) extraordinary growth in private veterinary schools of undetermined quality, (3) socioeconomic constraints on client engagement with preventive health care, (4) high regional prevalence of some key infectious diseases (e.g. feline leukaemia virus infection, canine visceral leishmaniosis), (5) almost complete lack of minimal antigen vaccine products as available in other markets, (6) relative lack of vaccine products with extended duration of immunity as available in other markets, (7) availability of vaccine products withdrawn from other markets (e.g. Giardia vaccine) or unique to Latin America (e.g. some Leishmania vaccines), (8) accessibility of vaccines directly by pet owners or breeders such that vaccination is not delivered under veterinary supervision, (9) limited availability of continuing education in veterinary vaccinology and lack of compulsion for continuing professional development and (10) limited peer‐reviewed published scientific data on small companion animal infectious diseases (with the exception of leishmaniosis) and lack of support for such academic research.
cord-257722-7rmzaau4	2019	Polymeric NPs are submicron-sized colloidal systems of natural or synthetic polymers used as delivery carriers of chemical drugs, proteins, peptides, and nucleic acids, owing to their high bioavailability, controlled release, biodegradable and biocompatible properties, and low toxic profiles [17] . Among the different polymers developed to formulate polymeric NPs, PLGA has won strong attention, owing to its attractive properties: biodegradability and biocompatibility, FDA and EMA approval in drug delivery systems for parenteral administration, well-described formulations and methods of production adapted to various types of drugs such as hydrophilic or hydrophobic small molecules or macromolecules, protection of the drug from degradation, the possibility of sustained release, the possibility of modifying surface properties to provide stealthiness and/or better interaction with biological materials, and the possibility of targeting NPs to specific organs or cells [29] .
cord-257899-l866puqk	2020	The authors concentrated on the use of flagellin, a potent inducer of innate immunity via toll-like receptor 5, as an adjuvant to formulate human immunodeficiency virus (HIV)-based nanoparticle B cell-targeting vaccines that display either the HIV-1 envelope protein (Env) or a model antigen, hen egg lysozyme (HEL). [6] discussed biomimetic nanoparticles (NPs) to deliver vaccines for the treatment of diseases including HIV, malaria, some tumors and bacterial diseases due to their beneficial advantages such as improved antigen stability, targeted delivery, long-time controlled release and evasion of immune responses. The authors showed the induction of specific cytotoxic T cell responses to HLA-A2-restricted and hepatitis B virus epitopes due to the ability of the filamentous rod, internalized into APCs. It seems likely that the targeted delivery of these NPs in new-generation vaccines against tumors such as melanoma and mastocytoma might be realized, although clinical trials are necessary to establish their safety in humans.
cord-258353-uw8padla	2020	[16] [17] [18] [19] In 2016, the American Academy of Pediatrics'' (AAP) Report "Countering Vaccine Hesitancy" characterized dismissal as acceptable only after careful consideration of the situation, transparency with parents about the risks to their child, and openness about practice policies. As an alternative to practice dismissal, there are several evidence-based tools in the provider-parent communication literature that can increase parental vaccine acceptance while keeping children of vaccine-hesitant parents in our practices. A multi-arm randomized trial in 30 pediatric and family medicine clinics across North Carolina found a 5.4% increase (95% CI; 1.1%-9.7%) in HPV vaccination coverage for patients in clinics whose providers received presumptive training, compared with conversation training or usual care. Evidence-based alternatives to dismissal exist, increase parental acceptance of vaccines, will keep under-vaccinated and unvaccinated children with pediatricians, and improve population health. As we work as pediatricians to improve the state of vaccine confidence, let us consider caring for vaccine-hesitant families, one visit at a time.
cord-258624-041cf99j	2020	title: Design of a Novel Multi Epitope-Based Vaccine for Pandemic Coronavirus Disease (COVID-19) by Vaccinomics and Probable Prevention Strategy against Avenging Zoonotics We identified non-structural protein 8 (Nsp8), 3C-like proteinase, and spike glycoprotein as potential targets for immune responses to COVID-19. In order to estimate the MMPBSA binding free energies for the receptors and multi-epitope peptide vaccine construct, the MMPBSA.py module [56] of AMBER16 was castoff. The B-cell epitopes predicted for the vaccine candidates were in the following order: nine for Nsp8 and 3C-like proteinase, five for Nsp9, eight for Nsp10, 34 for spike glycoprotein and surface glycoprotein, and four for ORF1ab polyprotein| partial. Molecular interactions and binding conformation of the designed MEPVC with TLR3 and TLR4 innate immune receptors were deciphered via a protein-peptide docking approach. The dynamic simulations of the human immune system in response to the designed vaccine construct were deciphered through C-immsim server [40] .
cord-258626-p469ysi8	2014	Criteria for assigning vaccines into these categories, and a third category, "generally not recommended," are based on: (1) morbidity and mortality associated with the specific disease (does the organism cause serious illness or does it cause a mild, transient disease that may pose only minimal risk to the individual or population?); (2) the prevalence and/or incidence rate of the disease (although a specific disease may not commonly be seen, the organism is ubiquitous in the environment and therefore poses risk to the individual or population); (3) the risk of the individual for exposure to the disease (indoor-only animal vs free-roaming individual, regional variations of occurrence); (4) the efficacy of the vaccine (does the vaccine prevent infection or simply ameliorate some signs or length of disease?); (5) the risks associated with administering the vaccine (are the risks associated with that vaccine greater than the risk of the disease?); (6) the potential for zoonotic disease; (7) the route of infection or transmissibility. 9, 13 The current recommendation is to use the CAV-II modified live virus product, as it stimulates the immune system to protect against both CAV-I and CAV-II, without the associated adverse reaction caused by the type I vaccine.
cord-259927-xh9cw9ao	2017	When considering prevention or treatment of viral respiratory tract infections, potential targets include the causative pathogens themselves but also the immune response, disease transmission, or even just the symptoms. Here we provide an overview of the options and highlight some of the most promising approaches in vRTI treatment, including symptomatic medication, immunomodulatory drugs, antiviral agents, and natural products, as well as in vRTI prevention, ranging from vaccines to immunostimulators and public health policies. Early in vivo evidence suggested that azithromycin has anti-inflammatory and antiviral effects through induction of interferon-stimulated gene mRNA expression and reduced viral replication and release in patients with asthma and chronic obstructive lung disease. mAb therapies to viral infections, such as EBV (rituximab) or RSV (palivizumab), provide passive immunization and are licensed, whereas similar agents targeting influenza and other viruses are in preclinical development.
cord-260956-w6wxsg4p	2017	When administered correctly to healthy birds, ND vaccines formulated with NDV of low virulence or viral-vectored vaccines that express the NDV fusion protein are able to prevent clinical disease and mortality in chickens upon infection with virulent NDV. Characterization of live LaSota vaccine strain-induced protection in chickens upon early challenge with a virulent Newcastle disease virus of heterologous genotype Protection from clinical disease against three highly virulent strains of Newcastle disease virus after in ovo application of an antibody-antigen complex vaccine in maternal antibodypositive chickens Antigenic differences among Newcastle disease virus strains of different genotypes used in vaccine formulation affect viral shedding after a virulent challenge Level of protection of chickens against highly pathogenic H5 avian influenza virus with Newcastle disease virus based live attenuated vector vaccine depends on homology of H5 sequence between vaccine and challenge virus
cord-261301-8mw2kpmr	2010	Nevertheless, both the effectiveness and imperfections of vaccination lead to the eventual global eradication of smallpox, and was the inspiration for development of the products and programs for immunization against several diseases in humans and animals. Table 1 describes the types of vaccines currently available to companion animal practitioners in most regions of the world 11-14 (http://www.aphis.usda.gov/animal_health/vet_biologics/ vb_licensed_products.shtml) These vaccines include very traditional inactivated antigen formulations, multiple attenuated agents, and new technologies such as poxvectored vaccines, defined subunit vaccines, and nucleic acid vaccines (see Table 1 ). Therefore, a well-differentiated antibody response with isotype switching, affinity maturation to high avidity, and memory requires some effective initial stimulation involving dendritic cells and expansion of regulatory T lymphocytes A claim that it is intended to prevent disease may be made only for products shown to be highly effective in preventing clinical disease in vaccinated and challenged animals.
cord-261566-fn08b0y2	2020	15 The disease severity and lung damage in the case of SARS-CoV-2 infection can be directly correlated with the dysregulated immune response at 7-10 days after symptom onset and is characterized by exuberant production of cytokines including IL-2, IL-7, IL-10, MIP-1A, IP-10, and TNF-α. 53, [98] [99] [100] [101] [102] Ferrets are a suitable animal model for SARS-CoV vaccine evaluation as they support viral replication in the respiratory tract, develop similar disease symptoms, and display severe lung pathology. Potential ADE and waning of vaccine-induced immune response represent other obstacles in the development of a mucosal vaccine against SARS-CoV-2. Intranasal vaccination of recombinant adeno-associated virus encoding receptor-binding domain of severe acute respiratory syndrome coronavirus (SARS-CoV) spike protein induces strong mucosal immune responses and provides long-term protection against SARS-CoV infection Effect of mucosal and systemic immunization with virus-like particles of severe acute respiratory syndrome coronavirus in mice
cord-261876-7rsc803x	2020	In considering the "certainty of success" in development of human coronavirus vaccines, particularly SARS-CoV-2, a third, related critical parameter is proposed—infectious inoculum intensity, at an individual-level, and force of infection, at a population-level. Reducing the infectious inoculum intensity (and force of infection, at a population-level) is predicted to lengthen the incubation period, which in turn is predicted to reduce the severity of illness, and increase the opportunity for an anamnestic response upon exposure to the circulating virus. The one factor that emerges for consideration in SARS-CoV-2 vaccine development and implementation is reducing the infectious inoculum intensity (and force of infection, at a populationlevel) to lengthen the incubation period, reduce the severity of illness, and increase the opportunity for an anamnestic response upon exposure to the circulating virus.
cord-262282-9xh51cd1	2020	
cord-263277-m4too6ob	2020	In their review article, the authors also presented a comprehensive summary of the current efforts to improve the influenza vaccines produced using standard existing technologies. In this particular context, animal studies support the potential of exploiting this strategy to generate universal or at least broader next generation vaccines providing heterosubtypic protection by stimulating long-lasting T cell resident memory cells. As described in the review, a universal vaccine based on peptides should mimic more closely the immune responses observed after natural infections by inducing both cross-reactive peripheral and tissue resident CD8 T cells in addition to cross-reactive antibodies and CD4 T follicular and helper cells. However, influenza vaccines based on both traditional and emerging technologies face the major constraint represented by the immune history of the individual vaccinees.
cord-263619-p17oomzn	2009	Although providing passive immunity to young infants, maternally acquired antibodies can interfere with the immune responses to the attenuated measles vaccine by inhibiting replication of vaccine virus. Women with vaccine-induced immunity tend to have lower antimeasles virus antibody titers than women with naturally acquired immunity, and their children may be susceptible to measles at an earlier age. The cumulative distribution can reach 50% by 1 year of age, with a significant proportion of children acquiring measles virus infection before 9 months, the age of routine vaccination. Infants and younger children, although susceptible if not protected by immunization, are not exposed to measles virus at a rate sufficient to cause a large disease burden in this age group. The only documented case of disease induced by vaccine virus in an HIV-infected person was in a 20-year-old man who died 15 months after receiving his second dose of measles vaccine ( Angel et al., 1998 ) .
cord-264356-3zu4w0a9	2020	Telehealth consultations have helped our institution provide continuity of care to older adults who would otherwise decline healthcare attendances due to fears of contracting COVID-19. Making vaccination a standard part of the LTCF admission process does increase vaccination rates in nursing homes, and it is recommended by the Department of Health and Human Services. These interactions make the facility vulnerable to infectious diseases, but one must not forget that living in LTCFs provides the residents with a comfortable environment, which makes them feel like being in one''s own home. However, when any vaccines that can prevent infection in elderly people are developed, vaccinating LTCF residents against COVID-19 should be a requirement. We should consider vaccine requirements for the elderly in LTCFs. Clinical characteristics and prognostic factors in COVID-19 patients aged ≥80 years Time to mandate influenza vaccination in health-care workers
cord-264571-rtac6hh2	2015	
cord-264814-v4wnmg03	2020	Herein, we review the current knowledge about the immune response to this novel virus as it pertains to the design of effective and safe SARS-CoV-2 vaccines and the range of novel and established approaches to vaccine development being taken. Herein, we review the current knowledge about the immune response to this novel virus as it pertains to the design of effective and safe SARS-CoV-2 vaccines and the range of novel and established approaches to vaccine development being taken. Comprehensive safety studies are particularly critical because some candidate vaccines use platform technologies that have not been examined extensively in human subjects to date, including some of the viral vectors, mRNA and nanoparticle constructs, and because of the potential for enhanced disease and adverse events related to aberrant immune responses to be seen upon infection pre-and post-licensure.
cord-265472-b1s4stvz	2015	In conclusion, there are several case reports of autoimmune diseases following vaccines, however, due to the limited number of cases, the different classifications of symptoms and the long latency period of the diseases, every attempt for an epidemiological study has so far failed to deliver a connection. We can infer that a similar response may be associated with different safety in relation to the development of autoimmune reactions to vaccines, particularly in the patients with genetic predisposition to an enhanced response to vaccine inoculation [85] . HSP was associated with seasonal influenza, influenza A (H1N1), pneumococcal and meningococcal disease, hepatitis A virus (HAV), HBV, anti-human papilloma virus (HPV) vaccines, and following multiple combinations of vaccines, such as typhoid, cholera and yellow fever [139, [171] [172] [173] . Hepatitis B vaccination and undifferentiated connective tissue disease: another brick in the wall of the autoimmune/inflammatory syndrome induced by adjuvants (Asia)
cord-265642-7mu530yp	2019	Using protein expression systems it is possible to produce virus-like particles (VLPs), which are made up of monomers, which are able to multimerize into VLPs, and display the antigenic determinants of target pathogens on their surface. For example, in different laboratories different eukaryotic systems for viral protein expression, including plant cells, are used to produce VLPs which are used for vaccination against the hepatitis C virus (HCV) [36] . Antigen of the duck hepatitis A virus produced in the baculovirus expression system assembles into VLPs immediately in the cultured Spodoptera frugiperda (sf9) cells, while immunization of ducklings with the obtained VLPs induces a high level humoral immune response and protects them from developing the disease [46] . Expression vectors for foreign protein production in plants have been developed based on plant viruses, which allows obtaining plant-producing recombinant viruses or VLPs displaying the target antigen on their surface [101, 102] .
cord-265757-8ces57rn	2009	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.
cord-266199-smlq11y9	2019	The economic burden caused by virus infections such as Porcine Reproductive and Respiratory Syndrome Virus, Swine influenza virus, Porcine Epidemic Diarrhea Virus, Porcine Circovirus 2, Foot and Mouth Disease Virus and many others are associated with severe morbidity, mortality, loss of production, trade restrictions and investments in control and prevention practices. Likewise, DCs targeted chitosan NPs loading plasmid DNA encoding nucleocapsid protein of Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) induced better nucleocapsid protein-specific mucosal IgA antibody response compared to soluble unentrapped antigens after nasal immunization in mice [57] . In this review, only studies conducted in pigs related to the development and evaluation of NPs-based vaccine candidates by using virus-like particles (VLPs), biodegradable polymers, polysaccharides and liposomes against porcine viral infections are included (Table 3) . Chitosan-based NPs are used in pigs to deliver adjuvants such as bee venom and plasmid encoding porcine IL-2 and IL-4/IL-6 genes, which improved induction of better virus-specific immune responses of respective vaccines against PRRSV and PCV2 [103, 104] .
cord-266202-3qku90ml	2020	
cord-266204-ipa017wz	2018	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] .
cord-266259-0f0guyea	2020	Infrastructure for safety surveillance Guidance for the clinical evaluation of vaccines is provided by large public health and regulatory authorities such as the WHO 6 . Routine surveillance for safety signals is based upon a statistical pair-wise analysis that detects disproportionality between the number of observed reports and the number of expected reports of a single adverse event for a single vaccine (such as febrile seizure for pneumococcal vaccine), followed by clinical validation and assessment of the case series for that vaccine and that AEFI. By contrast, within many low-income and middleincome countries, vaccines are largely administered by national immunization centres, which are also responsible for collecting data on AEFIs. Support to the national immunization programmes for safety surveillance has been provided by the Global Vaccine Safety Blueprint (GVSB) of the WHO 8 . Real-time global data exchange is essential as the pooling of reports of AEFIs into larger databases will allow for the earlier detection of safety signals.
cord-267012-45tre8rn	2018	While recombinant baculoviral vector expressing both VSV-G and influenza HA was shown to evoke both humoral and cellular immune responses and provided effective protection against lethal virus challenge in mouse and chicken hosts [26] , the high cytotoxicity of VSV-G protein [98] and its immediate inactivation by serum complement systems impedes the use of the element in a vaccine delivery vehicle [99] . The vaccine showed successful HA expression on its envelope, and mice vaccination studies showed that both the live and adjuvanted with inactive form of recombinant baculovirus induced HA-specific antibody responses and offered complete protection against lethal viral infection [101] . Moreover, recombinant baculovirus with CMV-polyhedrin dual promoter for expressing chimeric HA of H9N2 was shown to efficiently express HA in both mammalian and insect cells, induce strong immune response, and provide 100% protection against lethal H9N2 viral challenge in mice, unlike other vaccine candidates observed [34] .
cord-267666-i7uuf3ck	2020	Therefore, in this study, immunoinformatics methods were exploited to design a novel epitope-based subunit vaccine against the SARS-CoV-2, targeting four essential proteins of the virus i.e., spike glycoprotein, nucleocapsid phosphoprotein, membrane glycoprotein, and envelope protein. Thereafter, several in silico validations i.e., the molecular docking, molecular dynamics simulation (including the RMSF and RMSD studies), and immune simulation studies were also performed which predicted that the designed vaccine should be quite safe, effective, and stable within the biological environment. The MHC class-I and class-II epitopes were predicted from the target protein sequences for 503 constructing the vaccine. Exploring Leishmania secretory proteins 1232 to design B and T cell multi-epitope subunit vaccine using immunoinformatics approach Immunoinformatics approaches 1236 to explore Helicobacter Pylori proteome (Virulence Factors) to design B and T cell multi-epitope 1237 subunit vaccine. Immunoinformatics-guided designing of 1405 epitope-based subunit vaccine against the SARS Coronavirus-2 (SARS-CoV-2)
cord-267897-w4pbq2lb	2017	6 Vaccine preparations based on adsorption of the antigen onto a preformed aluminum hydroxide adjuvant are referred to as aluminum-adsorbed vaccines, in contrast to the alum-precipitated vaccines mentioned earlier. Here it was shown 42,43 that aluminum hydroxide had an inhibiting effect, whereas aluminum phosphate adjuvant augmented the immune response against the antigen encoded by the DNA nucleotide. In 2002, a group at University of Lausanne, headed by J€ urg Tschopp, defined the inflammasome as "a molecular platform triggering activation of inflammatory caspases and processing of pro-IL-b." 85 This initiated a new line of research leading to a possible explanation for the mechanisms of action of aluminum adjuvants in the early phases of the immune response with the stimulation and excretion of proinflammatory cytokines. Effect of the strength of adsorption of hepatitis B surface antigen to aluminum hydroxide adjuvant on the immune response
cord-268501-z4oztgi0	2020	In fact, by May 11th, 2020 seven vaccines had already entered Phase I clinical trials: (1) encapsulated mRNA encoding protein S (Moderna and NIAID, USA); (2) Adenovirus expressing protein S (Cansino Biologics, China); (3) DCs modified with lentivirus expressing several proteins and CTLs (Shenzen Geno-Immune Medical, China); (4) an APC modified with lentivirus expressing several viral proteins (35); (5) Inno 4800, SARS CoV2 DNA Injection (Innovio, USA); (6) ChAdOx1 vaccine from the Jenner Institute, Oxford University, (UK) which is a genetically modified Adenovirus expressing Coronavirus proteins (39) , and is also being tested in a Phase II trial; and finally (7) the whole inactivated coronavirus with Alum by Sinovac, China (40) . Furthermore, in vaccinated monkeys, seven days after infection, the Sinovac inactivated vaccine at 6 µg/dose induced high titers of IgG antibodies directed against the S, RBD and lower levels of anti-N protein antibodies, high titers of virus neutralizing antibodies with no detected antibodydependent enhancement of disease (ADE) (40) .
cord-269352-0o3mryu1	2008	Inoculation of plasmid DNA, encoding an immunogenic protein gene of an infectious agent, stands out as a novel approach for developing new generation vaccines for prevention of infectious diseases of animals. As an effective vaccine, plasmid DNA have a gene encoding a protective antigen of a pathogen, which when injected into host, is transcribed and translated, to induce a specific immune response. Regarding veterinary practice, the last few years have seen numerous trials of DNA vaccines against various animal diseases like foot and mouth disease (FMD) and herpes virus infection in cattle, Aujeszky''s disease and classical swine fever in swine, rabies and canine distemper in canines, and avian influenza, infectious bronchitis, infectious bursal disease and coccidiosis in birds (Oshop et al. Besides, DNA vaccines have been developed against major viral infections of poultry like avian influenza, utilizing the HA gene of the virus (Kodihalli et al.
cord-269448-1jikrn37	2008	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.
cord-269623-9pxdeva3	2003	The contrast between recent cases of H5N1 infection, associated with high mortality, and the typically mild, self-limiting nature of human infections with avian H7N7 and H9N2 influenza shows the gaps in our understanding of molecular correlates of pathogenicity and underlines the need for continuing international research into pandemic influenza. We gave priority to randomised controlled trials when available, to larger studies, articles published in high-impact journals that have a wide readership, and the systematic review and economic decision modelling, for the prevention and treatment of influenza, commissioned by the Health Technology Assessment Programme on behalf of the National Institute of Clinical Excellence. A meta-analysis of reports published before 2001 showed that vaccination reduces numbers of cases of influenza-like illness by 35%, hospital admissions for pneumonia and influenza by 47%, and all-cause mortality by 50%.
cord-269992-ruf0vvz4	2020	The development of an edible vaccine in a selected plant system has many significant advantages such as; easy and efficient oral delivery, low cost with higher scale production, avoidance of any trained medical personnel for delivery, lack of any pathogenic infection, multicomponent expression in a single plant, and so forth. Currently, the use of plant-based expression system platform have been extensively utilized for the expression and purification of vaccines, recombinant proteins, enzymes, and many bio-pharmaceuticals in a variety of plant species, including potato, corn, tomato, carrot, lettuce, and spinach and have reached at advanced stage of pre-clinical and clinical evaluation. The specific proteins can be expressed into desired plants with very less cost and can be grown to the required locations so that, an edible vaccine can be available to the needy population globally, especially in the developing countries. This novel technology provides the high and fast expression, purification, and better stability of desired proteins in to plant cells as well as their removal of refrigeration requirement and trained medical personnel for delivery.
cord-270709-jahnjvyk	2020	title: Large Simple Double-Blind Randomized Trials for the Rapid Assessment of the Effectiveness of COVID-19 Vaccines Large Simple Double-Blind Randomized Trials for the Rapid Assessment of the Effectiveness of COVID-19 Vaccines to the editor-The coronavirus disease 2019 (COVID-19) pandemic has brought not only far too many losses of human lives but an economic crisis as well. As all participants have been exposed, the effectiveness of a vaccine can be assessed with smaller sample sizes and possibly more quickly compared to the conventional trial with community participants; however, challenge studies are accompanied by serious ethical issues [3] . Among the advantages of using the LSRT design are that it allows central randomization of large numbers of volunteers within a short time and rapid collection of the relevant outcomes at a low cost compared to the conventional phase 3 trials with many follow-up visits and extensive monitoring.
cord-270998-1adloi3o	2020	There is a belief among veterinary practitioners and even educational institutions that the vaccines made in Brazil against canine distemper virus (CDV), canine parvovirus (CPV) and canine adenovirus (CAV) are ineffective or only partially effective. METHODS: The study was carried out at the Animal Protection Association and a total of 60 adult mongrel dogs were selected and divided into two groups. RESULTS: In group A, the Elevencell vaccine generated a protective antibody titre against CDV in 26 out of 28 subjects (92.85%), CPV in 24 out of 28 subjects (85.71%) and CAV in 26 out of 28 subjects (92.85%). Before immunization, both groups of animals presented results of ≤2 on the colorimetric scale, which means that all of them were eligible to take part in the vaccination protocol. Evaluation of the humoral immune response induced by vaccination for canine distemper and parvovirus: A pilot study
cord-271153-c0aw6jkz	2020	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.
cord-271250-ywb26cq6	2019	In-depth understanding of the role of adjuvants in activating the innate immune system, combined with systems vaccinology approaches, have led to the development of next-generation, novel adjuvants that can be used in vaccines against challenging pathogens and in specific target populations. Intact MyD88 signaling in each of the three types of APCs (DCs, macrophages and B cells) is essential for robust activity of TLR ligand-based vaccine adjuvants (PorB, a TLR2 ligand and CpG, a TLR9 ligand) such as induction of in vivo cytokine responses, germinal center (GC) formation and antibody production [49] . A combination adjuvant consisting of poly(I:C), a host defense peptide and PCEP when delivered intranasally transiently induces production of chemokines and cytokines in murine respiratory tissues, which promotes infiltration and activation of DCs, macrophages, and neutrophils to generate improved mucosal and systemic immune responses [55] .
cord-271528-ob4l0bcf	2020	In The Lancet, Denis Y Logunov and colleagues from the N F Gamaleya Research Institute of Epidemiology and Microbiology in Russia present findings from two phase 1/2, non-randomised, open-label studies of a heterologous, replication-deficient, recombinant adenovirus vector-based vaccine in both frozen and lyophilised formulations. In Logunov and colleagues'' studies, however, the threshold for neutralisation was set high in two regards: the inoculating viral dose was large, and no arising cellular damage was allowable. Safety and immunogenicity of an rAd26 and rAd5 vector-based heterologous prime-boost COVID-19 vaccine in two formulations: two open-label, non-randomised phase 1/2 studies from Russia Immunogenicity and safety of a recombinant adenovirus type-5-vectored COVID-19 vaccine in healthy adults aged 18 years or older: a randomised, double-blind, placebo-controlled, phase 2 trial Safety and immunogenicity of the ChAdOx1 nCoV-19 vaccine against SARS-CoV-2: a preliminary report of a phase 1/2, single-blind, randomised controlled trial
cord-272241-2fwz8z8n	2020	title: Exploring the SARS-CoV-2 structural proteins for multi-epitope vaccine development: an in-silico approach Hence, in this study, we have used immunoinformatic approaches to predict highly antigenic epitopes from SARS-CoV-2 structural proteins that would evoke a strong immune response in humans. For this purpose, we have used the structural proteins: Spike, Envelope, and nucleocapsid to predict B-cell, cytotoxic T lymphocyte (CTL) and helper T lymphocyte (HTL) epitopes for construction of vaccine. We have also performed the docking and molecular dynamic simulations (MDS) between the vaccine and human Toll-like Receptor-3 (TLR-3) to study their binding stability. The VaxiJen 2.0 server predicts the antigenicity of the multi-epitope vaccine peptide based on the physicochemical properties of the input protein. Whereas, ANTIGENpro server predicts the antigenicity of the multi-epitopic vaccine based on the protein microarray data analysis of the target organism. Three structural proteins (spike glycoprotein, nucleocapsid, and envelope) were selected to construct a multi-epitope vaccine, which is capable of eliciting the humoral and cell-mediated immune response.
cord-272512-gevrlcvy	2009	Mucosal immunity Vaccination Mannheimia haemolytica Cattle A B S T R A C T Recognition of the mucosal portal of entry for many infectious diseases and of the relevance of mucosal immune response to protection has encouraged the development of vaccines administered by mucosal routes, principally oral and intranasal, for stimulation of intestinal and nasopharyngeal lymphoid tissues respectively. An increase in anti-leukotoxin (Lkt) IgA was demonstrated in nasal secretions of calves following feeding of alfalfa expressing a truncated Lkt50 from Mannheimia haemolytica, and there is evidence suggesting that such vaccination may protect against experimentally induced pneumonia. An increase in anti-leukotoxin (Lkt) IgA was demonstrated in nasal secretions of calves following feeding of alfalfa expressing a truncated Lkt50 from Mannheimia haemolytica, and there is evidence suggesting that such vaccination may protect against experimentally induced pneumonia.
cord-273099-zkk5d6gd	2016	According to the authors, an integrated policy approach that preserves incentives for market entry and innovation in the vaccine industry while addressing parental vaccine concerns and increasing immunization funding and reimbursement for both providers and patients is needed. 2 Push strategies seek to address supply-side issues in the vaccine market by providing direct assistance to ease the burden of research, development, and production costs, whereas pull strategies are designed to manipulate demand for vaccines, thereby improving the likelihood of a return on investment by increasing the number of immunizations administered. The United Kingdom has taken a lead in promoting an International Financing Facility for Immunization (IFFIm) 69 IFFIm has raised more than $1 billion in capital markets to immunize poor children in developing nations against Reviews VACCINE POLICY vaccine-preventable diseases.
cord-273151-1h8c4yq9	2020	Several hundred COVID-19-specific vaccines are at various stages of development in academia and industry and make use of a variety of different generic platforms, such as inactivated virus, purified recombinant viral proteins with or without adjuvant, replicating and non-replicating viral vectored antigens, antigen-encoding DNA or mRNA. A phase 1, open-label trial in young adults showed acceptable safety and reactogenicity and the induction of neutralising antibodies after two injections 16 . Safety, tolerability, and immunogenicity of a recombinant adenovirus type-5 vectored COVID-19 vaccine: a dose-escalation, open-label, nonrandomized, first-in-human trial Immunogenicity and safety of a recombinant adenovirus type-5-vectored COVID-19 vaccine in healthy adults aged 18 years or older: a randomized, double-blind, placebo-controlled, phase 2 trial Safety and immunogenicity of the ChAdOx1 nCoV-19 vaccine against SARS-CoV-2: a preliminary report of a phase 1/2, single-blind, randomized controlled trial Phase 1/2 study of COVID-19 RNA vaccine BNT162b1 in adults Safety and immunogenicity of SARS-CoV-2 mRNA-1273 vaccine in older adults
cord-273526-ah0dvnxv	2017	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.
cord-274112-6t0wpiqy	2004	INTERPRETATION: The ability to produce a candidate reference virus in such a short period of time sets a new standard for rapid response to emerging infectious disease threats and clearly shows the usefulness of reverse genetics for influenza vaccine development. The agent must be handled only under conditions of at least biosafety level 3 (BSL3), and it can kill fertilised chicken eggs, the standard medium for the reassortment and Responsiveness to a pandemic alert: use of reverse genetics for rapid development of influenza vaccines propagation of influenza virus before its inactivation and formulation for use in vaccines. The vaccine-candidate reference virus stock described in this report has been produced entirely on a cell substrate licensed for the manufacture of human vaccine, and as such, is-to our knowledge-the first reverse genetically derived influenza vaccine suitable for testing in clinical trials. Recombinant influenza A virus vaccines for the pathogenic human A/Hong Kong/97 (H5N1) viruses
cord-274264-s477tw3x	2020	We evaluated the vaccine effectiveness and coverage required to suppress the COVID-19 epidemic in scenarios when social contact was to return to pre-pandemic levels and face mask use was reduced. But relaxing social distancing restrictions to the pre-pandemic level without changing the current face mask use would lead to a new COVID-19 outbreak, resulting in 0.8-4 million infections and 15,000-240,000 deaths across these four states over the next 12 months. In the state of California, if the current face mask use rate was maintained and the vaccine was weak, 50% coverage could avert 1 CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. However, the state of California, in particular, will need a vaccine coverage of close to 80% to suppress the COVID-19 epidemic, such that both social distancing restrictions and the requirement for face mask use can be relaxed.
cord-274756-nnm1n09a	2020	
cord-275031-0y0d4brz	2015	Live attenuated vaccines, in particular, miming best the "natural" infection, hold the advantage of eliciting the most complete and long-lasting immunization, are relatively inexpensive to produce, suitable to be distributed to large populations and do not require adjuvants. However, despite the repeated call from scientists and several valuable discoveries which could probably be transformed into treatments and vaccines [6] , the pharmaceutical companies showed limited interest in investing into MERS, as the disease kept a relatively low profile over the past three years and numerous other catastrophes fought simultaneously for economic and media attention. cruzi vaccines, these approaches do not provide a strong and long-lasting immunity against T. cruzi which can be used in combination with other techniques such as gene deletion or radiation to develop safe animal and human vaccines. cruzi infection and effective and safe drugs for treatment of Chagas disease.
cord-275033-y9z9l0ji	2020	For example, surveillance and studies of childhood infectious diseases provide the basis of morbidity and mortality data used to make J o u r n a l P r e -p r o o f Immunization was selected as an example for examination of epidemiology in informing public health policy and practice because childhood immunization is one of the ten greatest public health achievements in the United States--it saves lives and is cost-effective. Since public health authorities across the United States have needed to urgently implement non-pharmaceutical public health disease containment measures (e.g., shelter-in-place, postponements of noncritical health care visits), early epidemiological studies are already documenting a dramatic decline in ordering and administration of childhood vaccines, VFC clinic capacity to vaccinate children, and immunization coverage rates for VPDs.
cord-275210-baqaqsli	2007	Using the SAD Berne strain of virus adapted from the ERA strain, several types of MLV ORV vaccines have been produced for use in baits for free-ranging animals that serve as vectors for the maintenance and transmission of the disease in wildlife species . The new generation of vectored recombinant vaccines now appearing on the market, such as the avipoxvirus vaccine recently licensed for use for cats in the USA (a rabies glycoprotein, live canarypox vectored vaccine) appears to produce few, if any, allergic or neoplastic reactions (Greene and Dreesen, 1998; Greene and Rupprecht, 2006) . All currently licensed killed rabies vaccines intended for use in carnivores must protect 22 of 25 or 26 of 30 (or a statistically equivalent number) animals from an IM challenge with a rabies virus for 90 days post challenge and 80% of controls must die from the challenge (Code of Federal Regulations, 2004).
cord-275538-c44gmu22	2006	The current recommendation is to use the CAV-II MLV because it stimulates the immune system to protect against CAV-I and CAV-II without the associated adverse reaction caused by the type I vaccine [4, 14, 20] . There is a killed vaccine available; however, vaccination against this agent is typically not recommended, because most animals are not at risk to contract the parasite, the vaccine does not prevent infection (it may ameliorate clinical signs and decrease cyst shedding), and the disease is readily amenable to therapy (fenbendazole, albendazole, and metronidazole are off-label uses but commonly accepted as standard of care). Because the vaccine does not fully prevent infection and carries an association with adverse events that may be greater than the actual disease, routine vaccination of household pets with this product is generally not recommended.
cord-276193-cngz535o	2016	
cord-276209-5999g9gp	2020	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.
cord-276907-b855tj7x	2019	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] .
cord-278417-ty4wbtkv	2020	Keywords: Coronavirus, Covid-19, Vaccine, SARS-CoV-2 World Health Organisation discussed the "Top Threats to Human Health in 2019," and developed a strategic plan to meet the challenges. Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-Cov-2) has caused a pandemic of Coronavirus disease -19 (Covid-19) with global public health and economic crisis. Since the WHO notification of first case of this disease on 31st Dec, 2019 and a complete genome sequence of the virus on Jan 5, 2020, global attempts to produce a suitable vaccine are ongoing in scores of laboratories. Phase I: Vaccines are given to a limited number of human volunteers with emphasis on safety and also to monitor the immune response. RNA vaccine stimulates immune system to produce protective antibodies against viral S protein. Pandemic preparedness: Developing vaccines and therapeutic antibodies for COVID-19 The early landscape of COVID-19 vaccine development in the UK and rest of the world BCG-induced trained immunity: can it offer protection against COVID-19?
cord-279026-s3yx62u6	2020	Adverse events associated with vaccination that might compromise the health of an animal are usually rare, mild, and transient. Traditionally, adverse events resulting from vaccine administration have been reported by veterinarians to manufacturers or government agencies. It has, however, proved possible by examining the electronic medical records of a very large small animal general practice, to determine the prevalence of vaccine-associated adverse events in over a million dogs. The use of a standardized reporting system within a very large population has permitted objective analysis of the prevalence of adverse events occurring within three days of vaccine administration. Out of 1,226,159 dogs receiving 3,439,576 vaccine doses, 4678 adverse events were recorded (38.2/10,000 dogs); 72.8% of these events occurred on the same day the vaccine was administered, 31.7% were considered to be allergic reactions, 1.7% were classified as anaphylaxis, and 65.8% were considered "vaccine reactions" and were likely caused by innate immune responses.
cord-279260-tdvb0fhv	2020	It is also important to note that T-cell immunity was found to be elicited by SARS-CoV or MERS-CoV DNA vaccines (both express trimeric spike protein) [7, 9] . Determining which adjuvants can enhance protective vaccine response to SARS-CoV-2 will be important. For example, the MF59-adjuvanted influenza vaccine, Fluad, is only licensed and approved for adults aged 65 years and older, to elicit a higher protective immune response in the elderly This article is protected by copyright. To accelerate vaccine development, animal infection models for SARS-CoV-2 are needed. Although macaques show COVID-19-like disease upon SARS-CoV-2 infection, the non-human primate model is usually not readily accessible to most laboratories [27] . Expressing hACE2 through adenoviral transduction may provide another possible approach to generate a mouse model for SARs-CoV-2 infection. For example, a conserved CD4 T-cell epitope can mediate cross-reactive protection between SARS-CoV and MERS-CoV [38] .
cord-279629-t1xjy12y	2020	The present in silico study aimed to predict a novel chimeric vaccines by simultaneously targeting four major structural proteins via the establishment of ancestral relationship among different strains of coronaviruses. Hence, the study was designed to develop a chimeric recombinant vaccine against COVID-19 by targeting four major structural proteins of the pathogen, while revealing the evolutionary history of different species of coronavirus based on whole genome and protein domain-based phylogeny. Apart from the human coronaviruses, we introduced other coronaviruses which choose different species of bats, whale, turkey, rat, mink, ferret, swine, camel, rabbit, cow and others as host (Supplementary TableDomain analysis of spike protein of coronaviruses reveals that they contain mainly one signature domains namely, coronavirus S2 glycoprotein (IPR002552), which is present in all the candidates. Design of an epitope-based peptide vaccine against spike protein of human coronavirus: an in silico approach.
cord-280172-6o1gqe8v	2020	In this research, first, the CTL, HTL, and B-cell epitopes of the S protein were predicted using ProPred-1, ProPred, and ABCPred servers, respectively, and then were selected base on antigenicity, toxicity, allergenicity, and cross-reactivity with human proteomes. Next, the physicochemical properties of the construct were investigated, the 3D structure of the protein was predicted, and finally, its affinity to the MHC I and II molecules was investigated through docking, following that, was performed the molecular dynamics (MD) simulation of docking complexes. The antigenicity of the epitopes were calculated by VaxiJen v2.0 server (http://www.ddgpharmfac.net/vaxijen/VaxiJen/VaxiJen.html), which is based on the transformation of the protein sequences auto cross-covariance (ACC) into uniform vectors of main amino acid properties. selected N, M, and S proteins as the target antigen for the prediction of T and B-cell epitopes and designed a multi-epitope vaccine against SARS-CoV-2 [48] .
cord-280459-y0tbvs3t	2016	Yet developing vaccine delivery systems that induce humoral and cell-mediated response with mucosal immunity has been challenging to date. Nasal delivery of vaccines acts as a "first entry block," that is, blocks the pathogen entry, while invading to the mucosal surface by inducing local microbial-specific immune responses, thus increasing the general efficacy of the vaccine. The nasal route is considered an attractive route for vaccine administration with the following advantages: • Better patient compliance • Numerous microvilli present in the nasal epithelium provide a better absorption surface • Mucosal and systemic immune response can be induced • Easy immunization of large population groups • Nasal immunization does not require needles and syringes Many challenges stand in the way of developing nasal vaccines. Hence a polymer-based micro-/nanoparticulate system can be exploited as a viable nasal vaccine delivery system that is capable of delivering a multitude of antigens at the targeted sites and inducing desired immune response.
cord-282158-08u3x1z4	2013	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.
cord-282246-wyanwvxa	2020	During RV infection in human enteroid cultures [19] and in different species of mammals [20À25], different types of IFNs are secreted, and as will be discuss below, antiviral actions of these IFNs are actively countered in a host-range-specific manner by pathogenic RVs. Of the IFNs, type I IFN is mostly expressed in the intestinal hematopoietic cell compartment rather than in the epithelium where RV primarily replicates [26] . In addition, IFN sensitivity of RVs encoding full-length "functional" NSP1 proteins also occurs in specific cell lines, possibly reflecting NSP1''s inability to target host innate factors across different species [49] . Remarkably, in addition to these viral effects in infected cells, RV also potently inhibits STAT1 phosphorylation in uninfected bystander cells in response to different types of IFNs (5) . The active human IFN response to these heterologous RV vaccines suppresses their replication sufficiently to restrict pathogenicity and reactogenicity but not so much that the generation of effective RV immunity is suppressed.
cord-282360-byqhzyzi	2010	To overcome the potential problem of reversion to virulence of attenuated strain vaccine, subunit vaccines consisting of only one or a few ''subunit'' proteins of the pathogen that can stimulate immune responses directed at the intact virus have been developed using recombinant DNA technology. 21 have described a recombinant VP1 protein expressed in Escherichia coli BL21, showing that the VP1 protein with a complete adjuvant is able to elicit a neutralizing antibody response, enhance T helper cell proliferation, and induce high levels of interleukin (IL)-10 and interferon (IFN)-g in mice, providing direct evidence that the VP1 protein contains neutralizing epitopes independent of other viral capsid proteins; this paves the way for the use of VP1 as a backbone antigen for developing subunit vaccines against EV71. Protection against lethal enterovirus 71 infection in newborn mice by passive immunization with subunit VP1 vaccines and inactivated virus
cord-282507-swxs5pr1	2019	The second part of the review is related to phase I-III clinical trials of QS-21, mostly formulated in ASs, to evaluate efficacy, immunogenicity and safety of adjuvanted prophylactic vaccines against infectious diseases, e.g. malaria, herpes zoster, tuberculosis, AIDS and therapeutic vaccines against cancer and Alzheimer''s disease. They can act on one or more of the following targets to increase response to Ags: (1) sustaining release at the injection site (depot effect), (2) transient secretion of cytokines and chemokines, (3) recruitement of various immune cells (neutrophils, monocytes, eosinophils, macrophages and Dendritic Cells (DCs) at the injection site leading to a local immune-competent environment, (4) expression by the recruited APCs of various Pathogen Recognition Receptors (PRRs) both on their surface (Toll-like receptors, TLRs, C-type lectin receptors, CLRs), and intracellularly (Nucleotide Oligomerization Domain (NOD)-like receptors (NLRs) and Retinoic Inducible Gene-1 (RIG)-like receptors (RLRs)), which are recognized and/or activated by adjuvants, (5) maturation and activation of recruited APCs which up-regulate the expression of Major Histocompatibility Complex (MHC)-I and/or MHC-II and activation of co-stimulatory signals CD40, CD80/86, (6) increased capacity of APCs for Ag processing and presentation by MHC, (7) migration of the mature APCs to the draining lymph nodes (dLNs) to interact with Ag-specific B or T lymphocytes (through receptor-ligand interactions, MHC-T cell receptor (MHC-TCR), CD40-CD40L, CD80/86-CD28) which are activated to produce potent Ab-secreting B cells and/or effector CD8 + T cell responses (Awate et al., 2013) .
cord-283405-aozxvxxs	2018	
cord-283475-28900qlr	2018	
cord-285128-48l1w65p	2020	
cord-285613-hbd44euq	2009	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.
cord-285691-pceenwb6	2020	key: cord-285691-pceenwb6 title: Advances in skin science enable the development of a COVID-19 Vaccine cord_uid: pceenwb6 expressing adenovectors and adjuvant in the same MNAs resulting in a vaccine that induced both antibody responses and enhanced cytotoxic cellular immunity that is likely important for "universal" vaccines and cancer immunotherapies. Taken together, these and studies by others demonstrate the potential for the development of cutaneous immune engineering strategies to control systemic immune responses including the potential for developing novel vaccine strategies and immunotherapies, and even negative immunization strategies to treat systemic allergy and autoimmune diseases. Advances in skin biology are making important contributions to the fight against the COVID-19 pandemic demonstrating once again that dermatology is more than skin deep. Microneedles for drug and vaccine delivery Microneedle array delivered recombinant coronavirus vaccines: Immunogenicity and rapid translational development Improved cutaneous genetic immunization by microneedle array delivery of an adjuvanted adenovirus vaccine
cord-285760-y37ji92k	2020	
cord-285883-rlliacex	2020	These advances include production and purification methods, genetic incorporation of epitopes into the capsid so that mononuclear phagocytes present these antigens via major histocompatibility complex (MHC) class I and II pathways, cloaking the capsid with polymers/shields to prevent neutralization by antibodies (NAbs), retargeting the vector to professional antigen-presenting cells, using helper-dependent vectors (so that the vector-infected cell only expresses the target epitopes and not Ad antigens), using Ad types with a lower level of seroprevalence in some populations, and single-cycle replication of vaccines to produce massive amounts of antigens. When injected with a bolus of Ad antigens (the vaccine), the response includes re-activation of anti-Ad effector memory T cells (T EM s), which return via homing receptors to the mucosal environments-where most Ad infections occur-and increased production of antibodies. Few can argue with the preclinical data that demonstrate that Ad-based vaccines generate rapid, antigen-targeted immune response in mice, rabbits, hamsters, and monkeys.
cord-285982-1a5u7uux	2009	
cord-287067-rrsgl377	2008	
cord-287410-boxxlopy	2020	Band T-cell epitopes of the spike proteins have been predicted and designed into a multi-epitope vaccine construct. To predict the probable immune response of the designed multi-epitope vaccine construct in human immune system, in silico immune simulations were conducted using the C-ImmSim server (http://150.146.2.1/C-IMMSIM/index.php) (Rapin et al., 2010) . C-ImmSim is a novel in silico approach for the study of the mammalian immune system The tool is a combination of a mesoscopic scale simulator of the immune system with machine learning techniques for molecular-level predictions of major histocompatibility complex (MHC)-peptide-binding interactions, linear B-cell epitope discovery, and protein-protein potential estimation. The antigenicity of the vaccine construct including the adjuvant sequence and His-tag was predicted by the VaxiJen 2.0 server to be 0.6452 with a bacteria model at a threshold of 0.4.
cord-287824-zg5akivn	2020	title: Advanced drug delivery systems can assist in managing influenza virus infection: A hypothesis This article provides an insight into a novel hypothesis that describes how the integration of nanomedicine, with the development of drugs and vaccines can potentially enhance body immune response and the efficacies of anti-viral therapeutics to combat influenza infections. In the recent years, an 66 increasing trend of influenza outbreaks have been observed, prompting medical researchers to 67 design and develop suitable vaccines and novel therapeutic modalities [10] . Targeting 411 neutrophils using novel drug delivery systems in chronic respiratory diseases Increasing 440 complexity and interactions of oxidative stress in chronic respiratory diseases: An 441 emerging need for novel drug delivery systems Interactions 501 with the macrophages: An emerging targeted approach using novel drug delivery 502 systems in respiratory diseases Inhibition of H1N1 influenza virus infection by zinc oxide nanoparticles: 537 Another emerging application of nanomedicine
cord-287853-cob7ur35	2018	As illustrated in the following section and in Table 1 , mass spectrometry-based techniques have been used to perform the structural characterization, glycosylation profiling and antigen quantitation during the development of the HIV, influenza, Dengue, Ebola, Meningococcal, and other vaccines. The review also highlights that mass spectrometry-based methods such as glycan analysis has been used to analyze a specific envelope glycoproteins (Env) and has broad applicability to any other glycoprotein-based vaccines. 91 To improve on the conventional approaches for absolute quantitation of GP1 in Ebola virus-like particles (eVLPs), an isotope dilution full-scan liquid chromatography-high-resolution mass spectrometry method was developed using an UltiMate 3000 HPLC and an Development of a liquid chromatography high resolution mass spectrometry method for the quantitation of viral envelope glycoprotein in Ebola virus-like particle vaccine preparations Development and application of a reversed-phase high-performance liquid chromatographic method for quantitation and characterization of a Chikungunya virus-like particle vaccine
cord-288868-qfdxri93	2005	
cord-289360-h6wvx7gw	2015	journal: mBio Viruses account for up to 20% of all human cancers, and although a large percentage of new human papillomavirus (HPV) and HBV infections can now be prevented by vaccination, many are already infected, and the vaccines are not being used to their full potential. The tremendous reduction in mortality from such diseases as variola, measles, and rubella came about only because the causative viruses were identified, cultivated, attenuated, and made into effective vaccines by biomedical research. While we scientists cannot directly control funding or regulations, we can take charge of some aspects of the research enterprise in a way to ensure that it continues to benefit society. This requires engaging our elected officials both directly and indirectly by continuing to educate them and the public at large about the importance of fundamental research in infectious diseases.
cord-289535-srrfr1es	2020	
cord-289599-7vsynfgn	2020	The present article examines whether short-term, mid-term, and long-term vaccine safety can be achieved under such an accelerated schedule, given the myriad vaccine-induced mechanisms that have demonstrated adverse effects based on previous clinical trials and laboratory research. It is uncertain as to whether any of the drugs, vaccines, foods or radiation exposures of our predecessors, which were not tested for transgenerational effects, are adversely affecting human life at present. Of note, the question remains whether humanity is currently willing to pass on potential devastating diseases to future generations due to the present need for the speedy development of a vaccine, bypassing adequate long-term and transgenerational safety testing. The vaccine costs in this discussion are the potential adverse health effects from a cOVId-19 vaccine, particularly for the mid-and long-term. This least vulnerable demographic population would have to bear the brunt of any potential mid-and long-term adverse health impacts that may result from a vaccine inadequately tested for these effects.
cord-289763-jek2pd31	2020	
cord-289961-7q2wkwrf	2017	
cord-290004-v3ruj5bq	2020	
cord-290031-vffa1bu0	2020	These include changes to the timing and location of vaccine administration to accommodate social distancing, policies to ensure optimal management of public demand, access and uptake of available vaccines across the season, and the need for communications to be clear, frequent, and aligned among all stakeholder groups. Policy changes in Australia, together with strong communication from public health agencies and media reporting about the risk of coinfection and importance of influenza vaccination, generated significant demand for influenza vaccines early in the season. Policy changes and strong public education can potentially optimize influenza vaccine coverage as doses become available throughout the season but need to be sustained into future seasons to maintain vaccine uptake and achieve the required on-time supply of doses, including influenza vaccines that are specifically designed for certain populations.
cord-290705-7xkt6u73	2020	title: Evaluation of Passive Immunity Induced by Immunisation Using Two Inactivated gE-deleted Marker Vaccines against Infectious Bovine Rhinotracheitis (IBR) in Calves The results indicated that inactivated glycoprotein E (gE)-deleted marker vaccines are safe and produce a good humoral immune response in pregnant cattle until calving and PCD180. Regarding traditional vaccines, several reports have shown that cattle vaccinated with non-deleted modified-live vaccines transfer neutralising antibodies (NA) to the newborn calves that can protect them from experimental infection [12, 13] , and other studies have demonstrated that a poor titre of colostral antibodies increases the risk of contracting BoHV-1 infection in the calf [14] . In addition, the antibody titres observed in both the groups of newborn calves, born to the cattle immunised with vaccine A or B (0.85 log 10 and 0.75 log 10 , respectively), on PCD180 were lower than those required to protect them against infection by BoHV-1.
cord-291315-y40s45iv	2020	
cord-292528-8kdhf123	2009	
cord-293234-ouykx6g5	2012	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 ).
cord-293559-c78wcr8m	2020	
cord-294108-uvnh0s9r	2020	
cord-294347-axkdf5vu	2016	
cord-294366-swwz4kzd	2005	By definition of perceived need, we are most acutely aware of the requirement of effective vaccines against infectious agents, pathogens ancient, re-emergent and new, yet the opportunities for manipulation of immune responses offer potential in the prevention and treatment of a far larger diversity of diseases. For example, the level of protection required in a population (herd immunity) will be different and this could allow theoretical flexibility in vaccine efficacy.The application of molecular biology techniques can be crucial in the identification of new candidate antigens and subsequent determination of vaccine efficacy using adjuvants can feed knowledge back to correlates of protection in terms of immunological markers.This knowledge can then be used in choice of appropriate adjuvants and formulation.The key implication projected by this schematic is that for the greatest challenges in vaccine development the cyclical generation of knowledge provides a strong role for rational design.
cord-294789-07hto8qn	2020	
cord-294856-eeh2a0t8	2020	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.
cord-296469-h0ma163u	2016	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] .
cord-296831-wdpatr2z	2018	Earlier, we reported that a toll-like-receptor 7 (TLR7) agonist, resiquimod (R-848), stimulated the systemic immunity when adjuvanted with the inactivated Newcastle disease virus vaccine in the chicken. Here, we report the effect of R-848 when adjuvanted with live or inactivated avian infectious bronchitis virus (IBV) vaccines with special emphasis on mucosal immunity. R-848 enhanced the antigen specific humoral and cellular immune responses when co-administered with the vaccines as evidenced by an increase in the antibody titre in ELISA and stimulation index in lymphocyte transformation test (LTT) till 35 dpi and increased proportion of CD4(+) and CD8(+) T cells on 21 dpi in the flow cytometry. Co-administration of R-848 with live or inactivated IBV vaccine significantly increased the IgA response in the tear and intestinal secretion from 21 dpi, which was maintained till 35 dpi as compared to the vaccine alone group (P < 0.01).
cord-296839-b6bm8do1	2019	
cord-296886-0bma2749	2014	
cord-296967-qiil3gqk	2020	A novel concept in DNA vaccine design is the creation of an inhaled DNA plasmid construct containing a portion of the coronavirus spike protein for treatment and vaccination. An inhaled plasmid DNA vaccine replicates the route of lung infection taken by coronavirus with transfected cells secreting spike protein portions to induce immunity. 3 These findings of the identified spike proteins in the SARS-CoV-2 receptor binding domain and ACE2 region may provide useful information for treatment or vaccine development. 5 In this paper a series of inhaled plasmid DNA vaccine construct containing various forms of the coronavirus spike protein sequence may provide potential treatment and vaccine options as revealed by Yu et al. 3 Once in the lower respiratory tract or alveolar region of the lung deposited plasmid DNA will be taken up and expression of coronavirus spike proteins by host cells such as pneumocytes will occur.
cord-296998-ep46lzeo	2020	
cord-297131-3a9vjpvn	2018	
cord-297203-f3f31h4r	2019	
cord-299315-s43gw24k	2015	In this paper we propose One Health as a strategy to prevent zoonotic outbreaks as a shared goal: that human and Great Ape vaccine trials could benefit both species. Sure, while OH in this sense creates the grounds for humans to express compassion towards animals and ecosystems and to engage in novel approaches to health problems, overall it often achieves the same goals of prevention and response so far already installed in public health; so OH, in this sense, adds nothing to the ethical debate except by broadening the factors considered in any human cost-benefit analysis. Our proposal is for direct action to administer vaccinations to humans through public health and research paradigms, and additionally to animals to stave off future outbreaks in both populations. Such an approach, aimed at vaccinating animals in the first instance, would be preventative rather than reactive to an outbreak in human populations, by protecting across species and thereby creating a potential barrier to future occurrences of Ebola in the fauna.
cord-301577-3qc56c7d	2014	
cord-301876-d2j9wpqk	2020	Few groups have designed subunit vaccines against SARS-CoV-2; however, their workflow involved either use of single protein for vaccine design [24, 25] or used only CTL epitopes without considering the importance of B-cell or HTL epitopes [26] . B-cell epitopes for the screened SARS-CoV-2 proteins were predicted using the ABCPred server (http://crdd.osdd.net/raghava/abcpred/). A total of 6 HTLs, 18 CTLs, and 9 B-cell epitopes derived from the three proteins were used to design the subunit vaccine (566 amino acid residues) against SARS-CoV-2 (Supplementary Figure 1) . Based on extensive bioinformatics analysis, we used three proteins to design a multi-epitope subunit vaccine against novel coronavirus SARS-CoV-2. Computational studies suggest that our multi-epitope based subunit vaccine has a probability of showing good protective efficacy and safety against SARS-CoV-2 infection in humans. Development of epitope-based peptide vaccine against novel coronavirus 2019 (SARS-COV-2): Immunoinformatics approach
cord-302082-aaokc182	2011	
cord-302155-hksmt48i	2019	
cord-302222-9ad0fw6z	2013	
cord-302247-moor7dfc	2001	Kittens younger than 16 weeks of age are generally more susceptible to infection than are adult cats and typically develop more severe disease. 47 Immunity conferred by feline panleukopenia vaccines is considered to be excellent, and most vaccinated animals are completely protected from infection and clinical disease. If a susceptible cat is born into or is entering an environment in which viral upper respiratory tract disease is endemic (e.g., some catteries, boarding facilities, shelters), the use of a topical product may be advantageous. Manufacturers are required by the US Department of Agriculture to establish, by means of experimental challenge exposure studies, the minimum duration of immunity for the rabies virus vaccines that they sell, and products approved for use every year or every 3 years are available. Vaccination may be considered for cats in multiple-cat environments, where infections associated with clinical disease have been confirmed.
cord-302268-dmb0293x	2015	Immunologic adjuvants are essential for enhancing vaccine potency by improvement of the humoral and/or cell-mediated immune response to vaccine antigens. Immunologic adjuvants are essential for enhancing vaccine potency by improvement of the humoral and/or cell-mediated immune response to vaccine antigens. Vaccines made from live-attenuated or inactivated pathogens can elicit robust protective immune responses because those vaccines contain naturally occurring adjuvants. A benefit of using AS04 adjuvant in human vaccines is the effective induction of robust Th1-type immune responses by promoting IL-2 and IFN-γ production, which cannot be achieved by using alum alone. Thus, flagellin fusion proteins are suitable adjuvants for the development of vaccines to induce robust antigen-specific immune responses. Main benefits of these adjuvants are induction of high and long-lasting antibody titer, induction of balanced Th1 and Th2 type immunity, and induction of CMI including cytotoxic T cell response (42) .
cord-303368-tzgql225	2020	
cord-303447-3a7jxl34	2005	
cord-303674-0xo2fiop	2019	
cord-303880-zv4nbz9p	2020	
cord-304188-1nm1tbig	2014	
cord-304472-mi5v6512	2020	A plausible hypothesis is that CYD-TDV may trigger an immune response to dengue in seronegative persons that predisposes them to a higher risk of severe disease, analogue to what is seen in natural secondary dengue infections [16] . Two chimeric live-attenuated dengue vaccines are now in Phase 3 trials: one developed by Takeda (TAK-003) and one by the National Institute of Allergy and Infectious Diseases (TV003/TV005) (Table 1) . To determine the ability of a single dose of the live attenuated tetravalent dengue vaccine TV003 to induce a suitable neutralizing antibody response, a placebo-controlled clinical trial was performed in 48 healthy adults who received 2 doses of vaccine or placebo administered 12 months apart. Robust and balanced immune responses to all 4 Dengue virus serotypes following administration of a single dose of a live attenuated tetravalent dengue vaccine to healthy, Flavivirus-naive adults
cord-305175-1wg0wodr	2020	
cord-305488-vk59ghjm	2017	
cord-305807-n3fs7533	2005	11 Then recognition that purified replication-defective Ads could be propagated on 293 cells without helper viruses paved the way toward intentional production of genetically modified Ads. 12 The popularity of Ad as a recombinant viral vector is largely due to the successful and safe immunization of millions of US military recruits in 1971 with enterically coated Ad4 and Ad7 as a prevention against acute respiratory disease (ARD) outbreaks. Gonin et al, 37 10 years ago, constructed a replicationdefective HAd5, containing the envelope protein ENV gene of FIV; however, despite the fact that an antibody response to pseudorabies virus in cats showed the potential of rHAd5 vectors to be used in this species, cats injected with 10 10.8 -10 11.8 of 50% tissue culture infectious dose (TCID 50 ) adjuvanted with montanide ISA 708 (water in nonmineral oil) or with montanide ISA 206 (double water/mineral oil/water) of this rAd did not develop detectable antibody response against ENV.
cord-306733-df36w6l7	2020	
cord-307899-427a7i3h	1989	Adenoviruses cause significant disease in dogs, foxes, and man, but have also been isolated from cattle, swine, goats, sheep, horses, turkeys, and chickens, where they produce mild infections, mainly associated with the respiratory and intestinal tracts. The latter modified the virus by serial passage in porcine and canine tissue cultures; the resulting vaccine immunized dogs and did not produce clinical signs of infection except for occasional corneal opacity similar to that caused by natural infection. The immunity produced by the attenuated live-virus CAV-1 vaccines is long lasting and has drastically reduced the incidence of the canine disease. The exception is human hepatitis A virus, which causes a serious disease and has one serotype; the development of both inactivated virus and attenuated live-virus vaccines is in progress (Hilleman et al., 1982; Provost et al., 1983) . An attenuated live-virus yellow fever vaccine was developed by passage of the virulent Asibi strain in mouse brain and cell culture until it had lost its pathogenicity for monkeys and man (Theiler, 1951) .
cord-309083-ew9cwiw0	2018	In this review, authors summarized six major cyprinid viral diseases, including koi herpesvirus disease (KHVD), spring viraemia of carp (SVC), grass carp hemorrhagic disease (GCHD), koi sleepy disease (KSD), carp pox disease (CPD) and herpesviral haematopoietic necrosis (HPHN). Challenge experiment reveals that the oral recombinant subunit vaccine can protect 50%-60% grass carp from infection and generate immunity against GCRV [199] . Oral vaccination is an effective way to induce mucosal immunity [215] and this strategy has shown a successful induction of the antiviral responses against viral diseases in different fish species [165] . Gene expression analysis of common carp (Cyprinus carpio L.) lines during cyprinid herpesvirus 3 infection yields insights into differential immune responses Recombinant lactobacillus expressing G protein of spring viremia of carp virus (SVCV) combined with ORF81 protein of koi herpesvirus (KHV): a promising way to induce protective immunity against SVCV and KHV infection in cyprinid fish via oral vaccination
cord-309555-1ksahg3o	2014	Although the respondents in this study represent a biased population of farmers, the findings indicate areas for future investigation in order to improve vaccination strategies in cattle in the UK. In order for disease control to be effectively achieved via vaccination, correct usage is required, which includes administering vaccines via the correct route, at the appropriate time and to a specified target group of animals (Responsible Use of Medicines in Agriculture Alliance (RUMA) 2012). Sixty-six per cent of respondents indicated that they or somebody else on the farm had discussed the use of the vaccine with the person who had supplied it in the past year, and cost was the most common topic for dairy as well as beef farmers (Table 3) .
cord-309999-izdl0f2i	2006	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.
cord-311112-cg7wqc0q	2014	
cord-311331-l7dehit8	2020	
cord-313911-lfn9ggg3	2006	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.
cord-314009-7t1bzc7f	2016	The modern definition of an adjuvant includes not only classical immune stimulators but also any aspects of particle size, shape, and surface chemistry that enhance vaccine immunogenicity. 71 A self-assembling nanofibrous hydrogel induced an antibody response when tested as a vaccine delivery platform, either alone or formulated with CpG adjuvant (TLR9 agonist) as a delivery system for recombinant hepatitis B surface antigen (HBsAg). 73, 74 For example, 165 nm-diameter liposomes assembled from cationic lipid, cationic polymer, and plasmid DNA were shown to target antigen to draining lymph nodes, resulting in enhanced DC activation and immunity. These particles were specifically designed to electrostatically interact with commercial hemagglutinin antigens to generate an influenza vaccine with enhanced immune responses compared with the hemagglutinin alone. Advax, a polysaccharide adjuvant derived from delta inulin, provides improved influenza vaccine protection through broad-based enhancement of adaptive immune responses
cord-315131-4yb2b70g	2005	
cord-315293-kng4z4kf	2020	
cord-315339-dcui85lw	2015	Although neutralizing antibodies directed against the HA globular head are highly efficient at preventing and clearing influenza virus infection, they can also FIGURE 3 In the memory phase, migratory lung DCs capture viral antigen retained on follicular DCs (FDCs) in tertiary lymphoid organs and present it to specific T cells in the respiratory draining lymph nodes. This explains why passively transferred IgG is effective at preventing severe disease from respiratory infections in experimental animals and why serum IgG antibodies are the main correlate of protection for parentally administered inactivated influenza vaccines in humans (Section Respiratory Virus Vaccines). Nasal administration of influenza vaccine with type I IFN was effective at inducing serum antigen-specific IgG2a and mucosal IgA antibody responses and at providing full protection against influenza virus challenge (Proietti et al., 2002) .
cord-315570-khm1veuv	2020	
cord-316534-ep7ezoko	2010	
cord-316893-jwjr67po	2019	
cord-317739-2wojtboi	2020	
cord-318272-spt0oea0	2020	''Nanovaccines'' have been explored to elicit a strong immune response with the advantages of nano-sized range, high antigen loading, enhanced immunogenicity, controlled antigen presentation, more retention in lymph nodes and promote patient compliance by a lower frequency of dosing. The role of different nanovaccines in activating various arms of immunity with an intent to abate the use of frequent booster doses as vaccines for tuberculosis, malaria, HIV (human immunodeficiency virus), influenza, and cancer are discussed. Polyanhydride-based nanoparticles encapsulating F1-V antigen when administered intranasally induced an immune response that persisted for 23 weeks and elicited a high anti-F1-V IgG1 antibody response post-vaccination and conferred long-lived protective immunity against Yersinia pestis infections compared to recombinant F1-V antigen [47] . Another interesting strategy for developing personalized biomimetic cancer nanovaccines is the use of cancer cell membrane coated virus for increased adjuvanticity, infectivity and oncolytic activities to generate a strong anti-tumor immune response.
cord-318593-ni84gzg5	2020	Experience gained in the development of vaccines for Ebola virus disease provide important lessons in the regulatory, clinical, and manufacturing process that can be applied to SARS-CoV-2 and other epidemic pathogens. Extraordinary efforts were made to advance this vaccine candidate through Phase 1, 2, and 3 clinical trials and the data generated in the context of the West African Ebola outbreak has supported its licensure by the US Food and Drug Administration (FDA), conditional authorization by the European Medicines Agency (EMA) and several African countries, along with prequalification by the WHO. Regulatory agency collaboration is critical for success From the start of the West African Ebola outbreak, the US FDA, EMA, and Health Canada worked closely with each other and with the National Regulatory Authorities of the impacted West African countries, sharing information about candidate vaccines that were being tested and reviewing the clinical protocols, available data, and benefit-risk profiles.
cord-318683-1yxurnev	2018	
cord-318983-rmvqf6s9	2020	In addition, when supplies are "insufficient for patients in the highest risk categories-those over 60 years of age or with coexisting conditions-then equality supports using random selection, such as a lottery, for vaccine allocation." 13 Younger people, whom the overall framework otherwise generally favors (as they stand to gain more life years, and societal investments such as education would otherwise be wasted) should be prioritized only if "epidemiologic modeling shows that this would be the best way to reduce viral spread and the risk to others." 14 Using a lottery for allocating scare vaccines in the general population, as proposed here, is one way of treating people equally, and it is certainly superior to a first-come-firstserved approach (or, perhaps more accurately, a let-me-usemy-connections-and-pointy-middle-class-elbows approach) that likely explains why better-off and whiter groups typically get tested more frequently for Covid-19 than lowerincome people and people of color, as noted above.
cord-319226-yvgvyif0	2020	
cord-321901-zpi7uis1	2006	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
cord-322913-sq9mq6f1	2020	The complex and still unclear immunopathological mechanisms of SARS-CoV-2 infection, together with the progressive age-related decline of immune responses, and the lack of clear correlates of protection, make the design of vaccination strategies for older people extremely challenging. The complex and still unclear immunopathological mechanisms of SARS-CoV-2 infection, together with the progressive age-related decline of innate and adaptive immune responses, and the lack of a clear correlate of protection, make the design of vaccination strategies for older people extremely challenging (Fig. 3 ).
cord-322955-7dw32xby	2020	
cord-323540-7b2mt1a8	2020	
cord-323710-cmbg0ty8	2016	
cord-323794-p3zjxo1h	2020	As COVID-19 vaccines are under development, public health officials and policymakers need to create strategic vaccine-acceptance messaging to effectively control the pandemic and prevent thousands of additional deaths. Methods: Using an online platform, we surveyed the U.S. adult population in May 2020 to understand risk perceptions about the COVID-19 pandemic, acceptance of a COVID-19 vaccine, and trust in sources of information. The purpose of our study is to describe the current vaccine acceptance landscape with aims to 1) predict COVID-19 vaccine acceptance using regularly available demographic information, 2) identify the most vulnerable populations, and 3) provide information for public health officials and politicians to develop messaging for all Americans, while targeting communities most in need. The best model to predict COVID-19 vaccine acceptance in our survey using demographic information that is readily available had age, gender, race, and education as explanatory variables with an area under the curve (AUC) of 72% (table 2; figure 4 ).
cord-324001-m7ys95z7	2010	
cord-324219-z1nigtb5	2003	A concept called reverse genetics has recently enabled researchers at the St Jude Children''s Research Hospital (http://www.stjude.org) to construct an experimental vaccine against H5N1, a potential pandemic influenza strain, in less than a month. This flu vaccine will be the first produced by reverse genetics to go into clinical trial, and the speed with which it was produced, comments Rino Rappuoli, Vice President of Vaccine Research at Chiron Corporation (http://www.chiron.com) ''could be critical if H5N1 turns out to be the next, long-overdue pandemic strain to emerge from the Far East''. For example, says Kawaoka, ''many companies are planning to use reverse genetics to produce attenuated flu strains to be used as live vaccines that should give more protection than current inactivated vaccines''. Several laboratories are engineering coronavirus genomes as vectors for vaccine development and gene therapy, says Enjuanes, so it should be possible to make vaccines for SARS by adapting the available infectious cDNA clones.
cord-324349-26uuczmi	2014	
cord-324690-82qsirnk	2020	Over the past decade, three different vaccine approaches have been implemented, possible correlates of protection identified, and two have moved through clinical evaluation to advanced clinical trials. Analysis of the correlates of protection seen in the non-human primate studies point to qualitatively different responses than those observed in RV144, and the trials are evaluating in silico designed immunogens to present the most globally conserved HIV sequences to trigger quantitatively superior CD8 + T cell responses [8, 9] . The Antibody Mediated Protection (AMP) trials are currently evaluating VRC01, the CD4 binding site targeted bNAb, to determine the ability of this single antibody to prevent HIV infection in women in Southern Africa and MSM and transgender persons in the Americas [13] . The authors thank the trial participants, community members, activists and researchers who have so willingly participated in the challenging work of HIV vaccine discovery and development.
cord-324829-0nz0qioh	2017	
cord-324911-6s7ubbxl	2019	
cord-325010-7qrht7uq	2008	
cord-325052-7vlxa0i7	2019	However, vaccines for pathogens which cause severe, but occasional, disease outbreaks in endemic pockets have suffered from a lack of commercial incentive for development to a clinical standard, encompassing Phase III clinical trials for efficacy. While approval of vaccines for diseases caused by such pathogens would Clinical and Experimental Immunology REvIEw ARtIClE Series Editor: E Diane williamson make a significant impact on disease outbreaks, taking niche vaccines into clinical development, including Phase III clinical trials for efficacy, requires a large investment in time and money. An alternative is to develop such vaccines to request US Emergency Use Authorization (EUA), or an alternative status in the United States, Canada and European Union (EU) making use of a considerable number of alternative regulatory mechanisms that are available prior to licensing, so that the products are deployable at the first indications of a disease outbreak.
cord-325141-x3txhjkr	2020	This study was carried out to ascertain Maltese healthcare workers'' hesitancy to a novel COVID-19 vaccine and correlate this with influenza vaccine uptake. This study was carried out to ascertain Maltese healthcare workers'' hesitancy to a novel COVID-19 vaccine and correlate this with influenza vaccine uptake. (9) This study was carried out in order to ascertain the degree of vaccine hesitancy in Maltese healthcare workers vis-à-vis a putative novel COVID-19 vaccine later this year, and correlate this with influenza vaccination uptake. The increased proportion of Maltese healthcare workers who plan to take the influenza vaccine this year when compared to last winter is probably due to increased awareness of respiratory viral illnesses in general in the wake of the COVID-19 pandemic. The proportions of those who are likely/undecided/unlikely (half, quarter, quarter respectively) to take a COVID-19 are similar to rates reported in other countries.(10) The higher male inclination to take the vaccine may be due to a combination of factors which could include the innate male propensity for perceived risk taking in the face of a novel vaccine.
cord-325300-wawui0fd	2000	No less important are organized programs to promote self protection, case finding, and effective treatment of infections to stop their spread to other susceptible persons (e.g., HIV, sexually transmitted diseases, tuberculosis, malaria). Very great progress has been made in infectious disease control by clinical, public health, and societal means since 1900 in the industrialized countries and since the 1970s in the developing world. The WHO in 1998 has declared hepatitis prevention as a major public health crisis, with an estimated 170 million persons infected worldwide (1996) , stressing that this "silent epidemic" is being neglected and that screening of blood products is vital to reduce transmission of this disease as for HIu HCV is a major cause of chronic cirrhosis and liver cancer. Varicella vaccine is now recommended for routine immunization at age 12-18 months in the United States, with catch-up for children up to age 13 years and for occupationally exposed persons in health or child care settings.
cord-325966-0g7a9s5z	2020	
cord-326614-cik3ino6	2020	These trials include a variety of viral targets, vaccine platforms, and adjuvants to boost the immune response to vaccination. Another vaccine utilized the full-length H5 HA protein in an oral recombinant adenovirus type 4 (Ad4) vectored vaccine, Ad4-H5-Vtn. Three clinical trials have enrolled 313 participants between 18 and 49 years of age to investigate this avian H5 influenza vaccine. Although results for the phase II trial have not been posted, a press release from Novavax stated that NanoFlu induced superior HAI antibody responses against homologous and drifted strains compared to the seasonal influenza vaccine. Evaluation of the immunogenicity and safety of different doses and formulations of a broad spectrum influenza vaccine (FLU-v) developed by SEEK: Study protocol for a single-center, randomized, double-blind and placebo-controlled clinical phase IIb trial Safety and immunogenicity of a plant-produced recombinant hemagglutinin-based influenza vaccine (HAI-05) derived from A/Indonesia/05/2005 (H5N1) influenza virus: A phase 1 randomized, double-blind, placebo-controlled, dose-escalation study in healthy adults
cord-326960-9phlylce	2015	
cord-327650-6afsk8ix	2020	However, other differences were observed as people with an educational level under the High School degree, those with a low or intermediate level of household income per consumption unit (HICU), and those feeling close to a Far-Right party, were more numerous to be certain they would refuse the vaccine. Also, people who did not feel close to any party and did not vote at the last presidential campaign were more likely to refuse the coronavirus vaccine following one main reason: they thought that a vaccine produced in a rush is too dangerous. To our knowledge, this is the first study of the effect of politicization on attitudes to vaccines in France, one of the most vaccine-hesitant countries in the world ( politicization in vaccine hesitancy has mostly been studied in the United States of America where political polarization has increasingly become an object of concern in the past 10 years.
cord-328557-f6o1aynz	2020	
cord-328698-eeg1k5a6	2020	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.
cord-328935-mn8r972x	2015	Studies of the potential of novel adjuvants to improve vaccine efficacy against genetically unstable, immune-subverting RNA viruses, such as porcine reproductive and respiratory syndrome virus in pigs, should assist in the control of pathogens with similar characteristics in other species. However, a recent study showed that an inactivated reassortant RV strain (CDC-9 strain) formulated with aluminum phosphate and administered systemically in gnotobiotic pigs resulted in induction of serum IgG antibody titers, coinciding with partial protection against shedding and diarrhea, suggesting that adjuvant may have stimulated local specific (gut IgA antibodies) or nonspecific immune responses, which were not assessed in this study (Wang et al., 2010) . Intranasal delivery of whole cell lysate of Mycobacterium tuberculosis induces protective immune responses to a modified live porcine reproductive and respiratory syndrome virus vaccine in pigs
cord-330342-i55czo8a	2020	OWS is a combined effort of both public and private sectors with oversight by the US Department of Defense, Department of Health and Human Services, FDA, and the Centers for Disease Control and Prevention, for the safe development and distribution of SARS-CoV-2 vaccines. The results of the combined phase trials were later published on September 4, and revealed good immunogenicity for both humoral and cell-mediated immune responses; however, further investigation is needed in order to determine how effective the vaccines will be in preventing COVID-19 disease (10) . Trump Administration Collaborates With Moderna to Produce 100 Million Doses of COVID-19 Investigational Vaccine to Produce Millions of COVID-19 Investigational Vaccine Doses HHS, DOD Collaborate With Novavax to Produce Millions of COVID-19 Investigational Vaccine Doses in Commercial-Scale Manufacturing Demonstration Projects HHS, DOD Partner With Sanofi and GSK on Commercial-Scale Manufacturing Demonstration Project to Produce Millions of COVID-19 Investigational Vaccine Doses
cord-330496-p3o6zkhf	2020	The age of the cat is critical considering the persistent effects that maternal antibodies have on early vaccination, whereas old age presents other significant issues. Vaccines that may be considered as noncore include those against bacterial diseases caused by Chlamydia felis and Bordetella bronchiseptica, in addition to the infections caused by feline leukemia virus (FeLV), feline immunodeficiency virus, and feline coronavirus (Box 14.1). Duration of immunity following feline leukemia vaccination appears to be about three years, therefore cats in high-risk situations should be boosted annually or every two years. In some cats however, tumors develop at the injection sites usually between three months and three years after vaccination. In addition to rabies and FeLV vaccines, injection site sarcomas have also been associated with administration of inactivated vaccines against feline panleukopenia, feline herpesvirus, and feline calicivirus.
cord-331217-uup16bhm	2005	In keeping with current standards, we urge that old smallpox vaccines that were made in animal skin and are still a key part of our strategic national stockpile be tested for adventitious infectious agents. However, if these old vaccines are to be considered valid parts of our national stockpile we should expect not only continuing testing of potency and sterility but also testing for adventitious agents with methods that reflect the standards of today. We were unable to find a comprehensive list of possible adventitious agents when ovine materials are used, as is the case for the Lister strain smallpox vaccine produced in Europe and old vaccine stocks held by some European countries for biologic defense. Concerns about the possible presence of adventitious agents in old smallpox vaccine stocks are amplified further by current concerns about prions and the zoonotic potential of prion diseases.
cord-332358-0t4uxmj2	2004	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.
cord-335948-qkfxfmxb	2011	• The selection process is highly coordinated and involves continual year‐round integration of virological data and epidemiological information by National Influenza Centres (NICs), thorough antigenic and genetic characterization of viruses by WHO Collaborating Centres (WHOCCs) as part of selecting suitable candidate vaccine viruses, and the preparation of suitable reassortants and corresponding reagents for vaccine standardization by WHO Essential Regulatory Laboratories (ERLs). • The selection process is highly coordinated and involves continual year-round integration of virological data and epidemiological information by National Influenza Centres (NICs), thorough antigenic and genetic characterization of viruses by WHO Collaborating Centres (WHOCCs) as part of selecting suitable candidate vaccine viruses, and the preparation of suitable reassortants and corresponding reagents for vaccine standardization by WHO Essential Regulatory Laboratories (ERLs). The continuing threat posed by avian H5N1, the aftermath of the 2009 H1N1 pandemic, the increased knowledge of influenza, and the development and availability of new technologies provide a timely opportunity to review the complex processes and issues involved in influenza vaccine virus selection and to identify potential areas for improvement.
cord-335960-biwnqa3f	2007	The authors discuss the preventive strategies for infectious disease in sport, including (1) a review of immunization recommendations and prophylaxis guidelines, (2) improvements in personal hygiene and prevention of spread of infectious organisms by direct contact, (3) insect-borne disease precautions, and (4) prevention of sexually transmitted diseases (STDs). Sports medicine physicians need to consider the following indications for immunizations (Tables 1 and 2) : (1) routine health maintenance; (2) catch-up immunizations for failed or missed immunizations; (3) immunizations of high risk groups (ie, splenectomy, chronic disease, immunocompromised); (4) travel to an endemic area; (5) close contact with an infected individual, or (6) recent potential exposure to an infectious agent. When athletes are known to be infected with hepatitis B, secondary prevention includes education on personal hygiene, appropriate management of open wounds, proper use of protective equipment, safe sex practices using a condom, and avoidance of intravenous blood transmission (eg, through needle sharing and illicit drug use).
cord-336730-hqgwj8vs	1997	title: Placebo-controlled evaluation of a modified life virus vaccine against feline infectious peritonitis: safety and efficacy under field conditions 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. Feline infectious peritonitis (FIP) is a normally fatal disease of cats caused by infections with feline coronaviruses (FCoV) which are antigenically related to a respiratory coronavirus strain of man (HCV 229E), transmissible gastro-enteritis virus (TGEV) of swine and canine coronaviruses13''. The aim of this study was to evaluate the efficacy and safety of a modified live virus vaccine in a double-blind study under field conditions in two cat populations with higher risk for FIP.
cord-337577-dqikrmk7	2016	In the elderly, measures of cell-mediated immunity, such as granzyme B levels in virus-stimulated peripheral blood mononuclear cells, may correlate better than serum antibody titers with vaccine-elicited protection (McElhaney et al., 2009 ). Whether cell-mediated effector mechanisms, mucosal antibody, or some other factor is primarily responsible for protection by live attenuated influenza vaccines or natural infection remains controversial despite several decades of study. A key finding has been that, among the neutralizing antibodies elicited in response to influenza virus, HIV, or RSV infection or immunization, some have remarkably broad specificity (Burton and Mascola 2015; Corti et al., 2013 Corti et al., , 2011 . The elucidation of Toll-like receptors as key sentry molecules that detect potential pathogens and recruit antigen-presenting cells for a subsequent antigen-specific response has enabled the rational design of a new generation of potential vaccine adjuvants (Wu et al., 2014) .
cord-339091-3xk2w0d2	2010	
cord-339152-wfakzb6w	2020	Ebola and Marburg hemorrhagic fevers, Lassa fever, Dengue fever, Yellow fever, West Nile fever, Zika, and Chikungunya vector-borne diseases, Swine flu, Severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), and the recent Coronavirus disease 2019 (COVID-19) are examples of zoonoses that have spread throughout the globe with such a significant impact on public health that the scientific community has been called for a rapid intervention in preventing and treating emerging infections. The occurrence of significant disease outbreaks-such as SARS (severe acute respiratory syndrome) originating in China in 2002 (8) , the 2009 H1N1 swine flu pandemic from Mexico (9) , MERS (Middle East respiratory syndrome) that occurred in Saudi Arabia in 2012 (10) , the West African outbreak of Ebola virus (EBOV) in late 2013 (11) , the Zika virus (ZIKV) outbreak originating in Brazil in 2015 (12) , the 2018 health emergence in Nigeria caused by Lassa virus (13) , and the ongoing Coronavirus disease 2019 (COVID19) pandemic (14) -has renewed interests in developing strategies to faster prevent, treat, and/or control emerging and re-emerging viruses with high epidemic potential.
cord-339726-eg0hajzl	2020	Novel research designs, particularly where such studies might be controversial as in the case of SARS-CoV-2 HCS, require especially careful ethical evaluation including rigorous risk-benefit assessments as well as timely, thorough, public engagement ( WHO Working Group for Guidance on Human Challenge Studies in COVID-19 2020; Bambery et al. To be ethically acceptable, SARS-CoV-2 HCS would need to have multiple risk minimization strategies in place, including (i) selection of low risk participants (e.g., healthy young adults 1 ), (ii) careful strain selection and development, (iii) careful titration of viral dose, (iv) early diagnosis and availability of all necessary medical care, (v) long-term follow-up of participants, (vi) compensation for any lasting harms, and (vii) stringent infection control including measures to protect and screen research staff for infection (WHO Working Group for Guidance on Human Challenge Studies in COVID-19 2020). Tensions between public health and vaccine research priorities: A comparative modelling assessment of the risks and benefits of SARS-CoV-2 vaccine field trials versus human challenge studies
cord-340042-intxyu46	2020	
cord-340516-9dfaqsv7	2020	We demonstrate that, compared to expression of the S1 domain or a stabilized spike antigen, the full length, wild-type spike antigen induces significantly higher neutralizing antibodies in the periphery and in the lungs, when the vaccine is administered mucosally. Here, we report the induction of neutralizing antibody (Nab), IgG and IgA antibody responses, and T cell responses in mice following immunization of rAd vectors expressing one or more SARS-CoV-2 antigens. We have previously demonstrated that an oral, tableted rAd-based vaccine can induce protection against respiratory infection and shedding following influenza virus challenge 15 as well as intestinal immunity to norovirus antigens in humans 12 . In summary, these studies in mice represent our first step in creating a vaccine candidate, demonstrating the immunogenicity of the construct at even low vaccine doses and the elucidation of the full-length spike protein as a leading candidate antigen to induce T cell responses and superior systemic and mucosal neutralizing antibody.
cord-340900-f2iuy9e1	2020	CONCLUSION: A COVID-19 vaccine would be rapidly available at a slightly increased risk for undetected late side effects or insufficient efficacy if compared with standard vaccine development schemes. Absence of structural homologies of antibody targets with protein structures normally present in humans, analogous to the still disputed induction of narcolepsia by the influenza vaccine Pandemrix due to a structural homology with the hypocretin receptor [3] I suggest exponential exposure starting with 10 healthy volunteers, testing of antibody responses and safety after 14 days; if no stoppers [lack of adequate (see points 1-3 above) antibody response, intolerable side effects] occur, the number of vaccinated people will be increased by tenfold in each subsequent step, in this case to the next cohort of 100 people. At stage 3 + (1000 + people) when primary efficacy has been established at the antibody level and safety is no issue to this point, volunteers living in countries with high infection rates should be vaccinated.
cord-340994-m7vazpq9	2020	Understanding the student''s perspective about the future COVID-19 vaccine and supporting their health engagement and consciousness may be useful in planning adequate response and multidisciplinary educational strategies—including the psychological perspective on vaccine hesitancy underlying factors in the post-pandemic period. Although preliminary, this finding suggests that vaccination attitude is not only influenced by the students'' level of health knowledge, but probably by other motivational and psychological factors, including the sense of individual responsibility for population health and the common sense about the value of civic life and social solidarity, as demonstrated by other studies on the COVID-19 pandemic and previous emergencies [1, 9] . We think that the strategy to achieve efficient synergy between healthcare professionals and the general public is to better improve medical education of students during university and beyond introducing dedicated multidisciplinary curriculum about vaccinations and preventive behaviours for all university students and in particular to those attending healthcare curricula, an issue that requires increased attention to mitigate and control the COVID-19 pandemic.
cord-342800-62jklwiy	2020	The RNActive ® vaccine platform designed by CureVac used co-delivered RNA and protamine complex as the adjuvant to induce Th1 T cell responses, and naked, unmodified, and sequence-optimized mRNA as the antigen to develop mRNA vaccines [54] . used LNP to deliver self-amplified RNA vaccines, which caused the mRNA expression level in mice to be significantly higher than that of naked mRNA, CD4 + , and CD8 + T cell immune responses were also effectively induced. Overall development steps of those vaccines are (1) constructing the core antigen-encoding mRNA sequence optimized or combined based on selected antigen(s) from the target pathogen; (2) trying and choosing a proper combination of mRNA construction type, adjuvants, carrier materials and the route of administration; (3) detecting in vivo expression of the encoded antigen and the level of elicited immune responses; (4) providing research and demonstrations of immune induction mechanisms.
cord-342819-p8wp6yvo	2013	
cord-342831-4qfe8kok	2015	Chitosan-based formulations have been found to orchestrate both cellular and humoral responses, and represent the most promising candidates for adjuvant and delivery systems for mucosal vaccines [37] . Recently, chitosan-based adjuvant systems have been proven to have mucoadhesive qualities and the unique ability to open the tight junctions between epithelial cells at natural portals, which stimulates a robust mucosal immune response by facilitating the transport of antigens via an alternative yet effective route for antigen delivery [5, 30, 39, 74, 75] . In pre-clinical and clinical research, chitosan and its derivatives have demonstrated low-toxicity, mucoadhesive capabilities, the ability to enhance the internalization of antigens by APCs, and immune-stimulatory properties, which makes them promising candidates for effective mucosal adjuvants [5] . Development and characterization of surface modified PLGA nanoparticles for nasal vaccine delivery: effect of mucoadhesive coating on antigen uptake and immune adjuvant activity
cord-343347-guciupc8	2015	
cord-343365-4y9fedcr	2013	The promise of gene therapy as a cure for the disease has fizzled out, and while new antimicrobials and other pharmaceuticals promise improved longevity and better quality of life, the average life span of a patient with cystic fibrosis is still at about 35 years. Several significant challenge areas include the diagnosis and treatment of certain specific infectious lung diseases, including viral lower respiratory infections caused by respiratory syncytial virus, rhinovirus, metapneumovirus, coronovirus, and enterovirus. The search for a vaccine for respiratory syncytial virus (RSV) has been ongoing for many years, but like the previous case of gene therapy in cystic fibrosis, this also has been a challenge to achieve. The current global strategies for the development of an RSV vaccine now target four areas: infants <6 months of age; infants >6 months of age and young children; pregnant women for whom passive immunization can be implemented; and the elderly, in whom RSV can also have significant morbidity [52] [53] [54] .
cord-343421-k1dqe4lk	2018	
cord-343448-xhm97wy2	2020	In brief, RNAi works through gene silencing, degrading the mRNA for a specific protein through the coordinated action of double-stranded RNA and a complex biochemical machinery it activates (Fig 1) . The spearhead is mRNA-1273, which encodes a prefusion-stabilized form of the spike (S) protein of SARS-CoV-2, developed at an unusually fast rate (first volunteer injected on Mach 16, only 65 days after the publication of the virus sequence) by Moderna, a biotech based in Cambridge, Massachusetts (https://www.modernatx.c om/). Multi-component proteins that would be impossible to target with other systems are accessible with RNA technology, as recently demonstrated by the generation of a multi-antigenic mRNA vaccine encoding human cytomegalovirus glycoproteins gB and pentameric complex (John et al, 2018) . CV9202, for example, is a mRNA encoding six antigens usually expressed in non-small-cell lung cancer (NSCLC), developed by CureVac, a biotech based in Tübingen, Germany (https://www.curevac.com/), in collaboration with Boehringer Ingelheim.
cord-344006-0iq9s94n	2020	
cord-344062-8xxu0orq	2020	key: cord-344062-8xxu0orq authors: Bozkurt, Hayrunnisa Bekis title: Is the impact of childhood vaccines on coronavirus disease 2019, which is moderate in pediatric patients, possible? date: 2020-07-31 journal: Clin Exp Vaccine Res DOI: 10.7774/cevr.2020.9.2.183 sha: doc_id: 344062 cord_uid: 8xxu0orq nan with COVID-19 are vaccinated and live in an area with high vaccine hesitation. Finally, we think that childhood vaccines can be effective in observing COVID-19 infection as a mild disease for pediatric population. However, we need more knowledge about the pandemic considering that pediatric cases may be helpful in shedding light on the treatment of the disease. Hayrunnisa Bekis Bozkurt https://orcid.org/0000-0001-8642-4872 Clinical features in pediatric COV-ID-19 Are children less susceptible to COVID-19? Measles, immune suppression and vaccination: direct and indirect nonspecific vaccine benefits Protection from SARS coronavirus conferred by live measles vaccine expressing the spike glycoprotein Nonspecific effects of vaccines and the reduction of mortality in children
cord-344162-8gbe6qo7	2020	
cord-344563-bjuvxpkc	2020	An inactivated vaccine based on the Sal. abortus equi BN-12 strain with the Bac. subtilis TNP-3 strain filtrate used as immunomodulator has been developed in order to prevent salmonella-induced equine abortion. The Sal. abortus equi BN-12 strain stored at the All-Russia State Research Institute for Control, Standardization, and Certification of Veterinary Preparations was used in order to develop a vaccine against the salmonella-induced equine abortion. The preclinical tests with the white mice and the industrial tests with the horses have proven that the inactivated Bac. subtilis TNP-3 strain vaccine against salmonella-induced equine abortion is an effective method to prevent infectious abortions. Therefore, the method developed by the authors for specific prevention of the salmonella-induced equine abortion with the inactivated vaccine used with the culture liquid based on the Bac. subtilis TNP-3 strain is a cost-effective measure that should be recommended for widespread adoption in the stud farming systems.
cord-344576-upsc9cf8	2016	In February this year, the World Health Organization declared that further to the then unconfirmed association between the virus and the clinical manifestations of microcephaly and also Guillain-Barré syndrome, the Zika epidemic was a "public health emergency of international concern". No anti-Zika therapy, vaccine or drug, is currently available and while the production of the former has now been prioritized by multiple funding agencies, the history of infectious disease vaccine development indicates that this may take several years to reach the market place. A more rapid spread of the virus via the intercontinental travel of infected persons is an additional concern, although for Zika to become established in a location distant to an endemic area requires local transmission of the initially imported focus of infection; this is dependent on the availability of the vector. Local transmission of Zika virus infection is possible in Australia but should be contained by current vector control measures
cord-344669-hw57silv	2010	
cord-344750-b9tndbg1	2020	
cord-345191-nabxpyw3	2020	
cord-345689-5ns1onkw	2009	
cord-348144-t0chpsuh	2005	
cord-348283-7xorq5ce	2020	
cord-348409-oxjd263z	2019	Areas covered: The architectural traits of filamentous viruses and their derivatives, IAVs, facilitate the display of specific antigenic peptides which induce antibody production to prevent or curtail infection. The creation of Random Peptide Libraries (RPL), where random oligopeptides are fused to major capsid proteins (gp3 or gp8) and displayed on individual inovirus clones creating a random variety of IAVs which can be used for vaccine design via epitope mapping using monoclonal or polyclonal antibodies. Through this breakthrough technology which was the subject matter of the Nobel Prize in Chemistry 2018 (see ''Expert Commentary'' below), inovriuses displaying oligopeptides mimicking antigens (or specific epitopes of an antigen) can be used to vaccinate hosts thus inducing the desired antibody production. Unlike previous studies, which used a single specific peptide fused to a inovirus, four different antigenic peptides were displayed by inoviruses in a cocktail of recombinant IAVs. The induction of a cellular response completely vaccinated 1/3 of the pigs in the study and reduced the number of cysticerci in all other pigs [61] .
cord-349249-jwvz1ux2	2019	
cord-349309-7xsbpid7	2020	title: The Brighton Collaboration standardized template for collection of key information for benefit-risk assessment of viral vector vaccines The Brighton Collaboration formed the Viral Vector Vaccines Safety Working Group (V3SWG) in October 2008 to improve the ability to anticipate potential safety issues and meaningfully assess or interpret safety data, thereby facilitating greater public acceptance when a viral vector vaccine is licensed [3] . Pursuant to this goal, the V3SWG developed a standardized template that the Coalition for Epidemic Preparedness Innovations (CEPI) and other key stakeholders could use to evaluate and communicate key considerations for the benefit-risk assessment of viral vectors and viral vector vaccines. When completing information on adverse effects in Sections 6 and 11, 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 postlicensure clinical studies [9] . The Brighton Collaboration standardized templates for collection of key information for benefit-risk assessment of vaccines by technology (BRAVATO; formerly V3SWG).
cord-350565-mejd7blb	2019	We next consider emerging paradigms in causal inference for infectious diseases, ranging from approaches to evaluating vaccines and antimicrobial therapies to the task of ascribing clinical syndromes to etiologic microorganisms, an age-old problem transformed by our increasing ability to characterize human-associated microbiota. We next consider emerging paradigms in causal inference for infectious diseases, ranging from approaches to evaluating vaccines and antimicrobial therapies to the task of ascribing clinical syndromes to etiologic microorganisms, an age-old problem transformed by our increasing ability to characterize human-associated microbiota. Although serosurveys have bolstered recent efforts to understand the geographic range and clinical spectrum of EBOV and Zika virus infections (47, 48) , the enhancement of dengue hemorrhagic fever risk by prior exposure (49) , and the role of immunologic history in influenza susceptibility and vaccine response (50) , there remain few examples of public health programs undertaking serological studies for routine surveillance, at least in civilian populations (51) .
cord-351190-sq6zsqqi	2020	
cord-351649-87g7g5au	2009	
cord-352088-9k01ej6l	2020	
cord-353730-owcapg8h	2014	
cord-353911-hp6s6ebh	2020	title: Early immune response in mice immunized with a semi-split inactivated vaccine against SARS-CoV-2 containing S protein-free particles and subunit S protein Our aim was to design a semi-split inactivated vaccine offering a wide range of multi-epitope determinants important for the immune system including not only the spike (S) protein but also the envelope, membrane and nucleocapsid proteins. The above laboratory procedure generated a semi-split inactivated vaccine, i.e., a vaccine with 307 the S protein separated from the viral particle exhibiting an early, both humoral and cellular, 308 immune response. Safety and immunogenicity of the ChAdOx1 nCoV-386 19 vaccine against SARS-CoV-2: a preliminary report of a phase 1/2, single-blind, 387 randomised controlled trial An in-depth investigation of the safety and immunogenicity of an 468 inactivated SARS-CoV-2 vaccine A double-inactivated 499 whole virus candidate SARS coronavirus vaccine stimulates neutralising and 500 protective antibody responses. Inactivated Vaccine Against SARS-CoV-2 on Safety and Immunogenicity 526
cord-354030-8tfg881h	2020	
cord-354068-4qlk6y7h	2012	Due to the difficulties in evaluating wild-type filovirus infection in small animals and the generally high level of immune protection correlates derived from non-human primate (NHP) models of infection, therapeutics and vaccines are ultimately evaluated in NHP species for efficacy against filovirus. In their study, a heterologous prime/boost strategy with recombinant adenovirus serotypes 26 and 35 carrying GP (Z) and GP (S/G) demonstrated complete protection among NHPs. Each of these vectors was capable of stimulating humoral and cell-mediated immune responses in the context of NHPs pre-vaccinated with rAd5 as evidenced by antibody titers reaching an order of magnitude above those achieved in rAd5 vaccinated subjects (1:32,000 compared to 1:6,800), and CD8 + intracellular cytokine staining was 4.7-fold greater among heterologous prime/boosted subjects (0.41% compared to 0.09%) [59] . This GP-Fc fusion protein induced both cell-mediated and humoral immune responses, and mice vaccinated with ZEBOVGP-Fc demonstrated 90% protection against a lethal EBOV challenge.
cord-354972-nc496v6s	2020	As of 8 August 2020, there have been over 1.2 million confirmed cases of COVID-19 in Africa, with 29,833 deaths reported (Africa CDC) There is concern that the pandemic may pose an even greater risk to countries in Africa owing to their weak health-care infrastructure, large burden of co-infections, including HIV-1 and tuberculosis, and ongoing outbreaks of emerging and re-emerging infections such as Ebola virus (Democratic Republic of Congo) and Lassa haemorrhagic fever (Nigeria) that will divert much-needed resources away from the fight against COVID-19 (ref. Given the optimistic development timeline of 12-18 months before any vaccines could be available for widespread use, it is clear that these efforts will not Box 1 | Potential impact of climate on SArS-coV-2 dissemination the comparatively low incidence of coronavirus disease-2019 (COviD19) in africa has raised the possibility that climate could influence the spread of severe acute respiratory syndrome coronavirus 2 (sars-Cov-2).
cord-355541-5sctqkwr	2005	
cord-355618-7kfxc2w1	2020	In his statement of support 7 , the WHO Director-General Dr. Tedros Ghebreyesus asserted that "These online efforts must be matched by tangible steps by governments and the health sector to promote trust in vaccination and respond to the needs and concerns of parents." In order to adequately respond to these needs and concerns, which differ depending on the cultural, societal, and personal beliefs of a particular region, the WHO recommends that each country take steps to develop an understanding of vaccine hesitancy at a local level on an ongoing basis 8 . In recognition of these missed opportunities and in response to declining immunization rates and increasing national skepticism on the safety of vaccines, Congress has introduced bipartisan legislation to expand research into vaccine hesitancy. The bipartisan VACCINES Act is an important step in supporting evidence-based research into vaccine hesitancy. Association between vaccine refusal and vaccine-preventable diseases in the United States: a review of measles and pertussis
cord-355689-mo4mvwch	2019	
cord-355906-yeaw9nr8	2015