scholarly journals Assessment of immunogenicity and protective efficacy of ZyCoV-D DNA vaccine candidates in Rhesus macaques against SARS-CoV-2 infection

2021 ◽  
Author(s):  
Pragya D Yadav ◽  
Sanjay Kumar ◽  
Kshitij Agarwal ◽  
Mukul Jain ◽  
Dilip R Patil ◽  
...  
Keyword(s):  
Vaccine Candidate ◽  
Protective Efficacy ◽  
Rhesus Macaques ◽  
Herd Immunity ◽  
Lavage Fluid ◽  
Injection System ◽  
Protective Measure ◽  
Vaccine Candidates ◽  
Virus Challenge ◽  
Syringe Needle

AbstractVaccines remain the key protective measure to achieve herd immunity to control the disease burden and stop COVID-19 pandemic. We have developed and assessed the immunogenicity and protective efficacy of two formulations (1mg and 2mg) of ZyCoV-D (a plasmid DNA based vaccine candidates) administered through Needle Free Injection System (NFIS) and syringe-needle (intradermal) in rhesus macaques with three dose vaccine regimens. The vaccine candidate 2mg dose administered using Needle Free Injection System (NFIS) elicited a significant immune response with development of SARS-CoV-2 S1 spike region specific IgG and neutralizing antibody (NAb) titers during the immunization phase and significant enhancement in the levels after the virus challenge. In 2 mg NFIS group the IgG and NAb titers were maintained and showed gradual rise during the immunization period (15 weeks) and till 2 weeks after the virus challenge. It also conferred better protection to macaques evident by the viral clearance from nasal swab, throat swab and bronchoalveolar lavage fluid specimens in comparison with macaques from other immunized groups. In contrast, the animals from placebo group developed high levels of viremia and lung disease following the virus challenge. Besides this, the vaccine candidate also induced increase lymphocyte proliferation and cytokines response (IL-6, IL-5).The administration of the vaccine candidate with NFIS generated a better immunogenicity response in comparison to syringe-needle (intradermal route). The study demonstrated immunogenicity and protective efficacy of the vaccine candidate, ZyCoV-D in rhesus macaques.

scholarly journals Immunogenicity and protective efficacy of inactivated SARS-CoV-2 vaccine candidate, BBV152 in rhesus macaques

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Pragya D. Yadav ◽  
Raches Ella ◽  
Sanjay Kumar ◽  
Dilip R. Patil ◽  
Sreelekshmy Mohandas ◽  
...  
Keyword(s):  
Vaccine Candidate ◽  
Histopathological Examination ◽  
Protective Efficacy ◽  
Rhesus Macaques ◽  
Alveolar Epithelium ◽  
Neutralizing Antibody ◽  
Lavage Fluid ◽  
Phase Iii ◽  
Health Crisis ◽  
Vaccine Candidates

AbstractThe COVID-19 pandemic is a global health crisis that poses a great challenge to the public health system of affected countries. Safe and effective vaccines are needed to overcome this crisis. Here, we develop and assess the protective efficacy and immunogenicity of an inactivated SARS-CoV-2 vaccine in rhesus macaques. Twenty macaques were divided into four groups of five animals each. One group was administered a placebo, while three groups were immunized with three different vaccine candidates of BBV152 at 0 and 14 days. All the macaques were challenged with SARS-CoV-2 fourteen days after the second dose. The protective response was observed with increasing SARS-CoV-2 specific IgG and neutralizing antibody titers from 3rd-week post-immunization. Viral clearance was observed from bronchoalveolar lavage fluid, nasal swab, throat swab and lung tissues at 7 days post-infection in the vaccinated groups. No evidence of pneumonia was observed by histopathological examination in vaccinated groups, unlike the placebo group which exhibited interstitial pneumonia and localization of viral antigen in the alveolar epithelium and macrophages by immunohistochemistry. This vaccine candidate BBV152 has completed Phase I/II (NCT04471519) clinical trials in India and is presently in phase III, data of this study substantiates the immunogenicity and protective efficacy of the vaccine candidates.

scholarly journals Remarkable immunogenicity and protective efficacy of BBV152, an inactivated SARS-CoV-2 vaccine in rhesus macaques

2020 ◽  
Author(s):  
Pragya Yadav ◽  
Raches Ella ◽  
Sanjay Kumar ◽  
Dilip Patil ◽  
Sreelekshmy Mohandas ◽  
...  
Keyword(s):  
Histopathological Examination ◽  
Protective Efficacy ◽  
Rhesus Macaques ◽  
Alveolar Epithelium ◽  
Neutralizing Antibody ◽  
Lavage Fluid ◽  
Effective Vaccine ◽  
Phase I Clinical Trials ◽  
Health Crisis ◽  
Vaccine Candidates

Abstract The COVID-19 pandemic is a global health crisis that has severely affected mankind and posed a great challenge to the public health system of affected countries. The availability of a safe and effective vaccine is the need of the hour to overcome this crisis. Here, we have developed and assessed the protective efficacy and immunogenicity of an inactivated SARS-CoV-2 vaccine (BBV152) in rhesus macaques (Macaca mulata). Twenty macaques were divided into four groups of five animals each. One group was administered a placebo while three groups were immunized with three different vaccine candidates at 0 and 14 days. All the macaques were challenged with SARS-CoV-2 fourteen days after the second dose. The protective response was observed with increasing SARS-CoV-2 specific IgG and neutralizing antibody titers from 3rd-week post-immunization. Viral clearance was observed from bronchoalveolar lavage fluid, nasal swab, throat swab, and lung tissues at 7 days post-infection in the vaccinated groups. No evidence of pneumonia was observed by histopathological examination in vaccinated groups, unlike the placebo group which showed features of interstitial pneumonia and localization of viral antigen in the alveolar epithelium and macrophages by immunohistochemistry. Data from this study substantiate the immunogenicity of the vaccine candidates and BBV152 is being evaluated in Phase I clinical trials in India (NCT04471519).

scholarly journals Myths Surrounding Covid-19 Vaccine Candidates: A Guide to Fight Back

2021 ◽  
Author(s):  
John Zizzo
Keyword(s):  
Public Health ◽  
Herd Immunity ◽  
Vaccine Uptake ◽  
Protective Measure ◽  
Vaccine Hesitancy ◽  
Health Providers ◽  
Vaccine Candidates ◽  
The Public ◽  
News Organizations ◽  
Public Health Officials

The Covid-19 pandemic has propelled public health officials into the socio-political sphere due to the need for constantly updated information on behalf of the public. However, many individuals choose to acquire health information/guidance from indirect sources, including social media, news organizations, and general word of mouth. As a result, myths and false narratives about various essential health topics, including vaccine characteristics and protective measures, can circulate un-verified between millions of individuals with little recourse. These can further widen the “gap” between public knowledge and current research, resulting in lower vaccine uptake (vaccine hesitancy) and protective measure adherence. Such actions have profound implications as nations attempt to achieve herd immunity and end the pandemic once and for all. Thus, it is vital that public health officials, health providers, researchers, and the general public be able to differentiate common Covid-19 myths from facts and be prepared to approach such interactions via sound reasoning and research-based evidence. This chapter will serve as a guide to accomplish just that.

scholarly journals Investigation of the antigenicity and protective efficacy of Leishmania promastigote membrane antigens in search of potential diagnostic and vaccine candidates against visceral leishmaniasis

2019 ◽  
Author(s):  
Sarfaraz Ahmad Ejazi ◽  
Smriti Ghosh ◽  
Anirban Bhattacharyya ◽  
Mohd Kamran ◽  
Sonali Das ◽  
...  
Keyword(s):  
Visceral Leishmaniasis ◽  
Vaccine Candidate ◽  
Protective Efficacy ◽  
Indian Subcontinent ◽  
Murine Models ◽  
Past Infection ◽  
Vaccine Candidates ◽  
Membrane Antigens ◽  
Human Use ◽  
New Biomarkers

Abstract BackgroundVisceral leishmaniasis (VL), a parasitic disease causes serious medical consequences if treatment is delayed. Despite a decline in the number of VL cases in the Indian Subcontinent, commencement of the disease in newer areas continues to be a major concern. Although serological diagnosis mainly by immunochromatographic tests has been found to be effective, test for cure in different phases of treatment is still desired. Even though good prophylactic response has been obtained in murine models by a number of vaccine candidates, few have been proposed for human use. MethodsIn this study, nine antigenic components (31, 34, 36, 45, 51, 63, 72, 91 and 97 kDa) of Leishmania promastigote membrane antigens, LAg, were electroeluted and evaluated through ELISA to diagnose and distinguish active VL from one month cured and six month past infection. Further, to investigate the immunogenicity of electroeluted proteins, humans PBMCs of cured VL patients were stimulated with 31, 34, 51, 63, 72, and 91 kDa proteins.ResultsWe found that 34 and 51 kDa fractions show 100% sensitivity and specificity with healthy controls and other diseases. After six months post treatment antibodies to 72 and 91 kDa antigens show a significant decline to almost normal levels. This suggests that 34 and 51 kDa are efficient in diagnosis whereas 72 and 91 kDa may be used to monitor treatment outcome. In another study, 51 and 63 kDa proteins demonstrated maximum ability for up-regulate IFN-g and IL-12 with minimum induction of IL-10 and TGF-β. The results indicating that 51 and 63 kDa proteins could be strong candidates for human immunization against VL. In contrast, 34 and 91 kDa demonstrated a reverse profile and may not be a good vaccine candidate. ConclusionsThe present study accounts our search for new biomarkers for tests of clinical cure as well as effective immunoprophylactic candidates for VL vaccination.

scholarly journals Immunogenicity and protective efficacy of one- and two-dose regimens of the Ad26.COV2.S COVID-19 vaccine candidate in adult and aged rhesus macaques

2020 ◽  
Author(s):  
Laura Solforosi ◽  
Harmjan Kuipers ◽  
Sietske K. Rosendahl Huber ◽  
Joan E.M. van der Lubbe ◽  
Liesbeth Dekking ◽  
...  
Keyword(s):  
Single Dose ◽  
Vaccine Candidate ◽  
Protective Efficacy ◽  
Rhesus Macaques ◽  
Vaccine Dose ◽  
Neutralizing Antibody ◽  
Antibody Responses ◽  
Upper Respiratory Tract ◽  
Post Dose ◽  
Early Indication

AbstractSafe and effective coronavirus disease (COVID)-19 vaccines are urgently needed to control the ongoing pandemic. While single-dose vaccine regimens would provide multiple advantages, two doses may improve the magnitude and durability of immunity and protective efficacy. We assessed one- and two-dose regimens of the Ad26.COV2.S vaccine candidate in adult and aged non-human primates (NHP). A two-dose Ad26.COV2.S regimen induced higher peak binding and neutralizing antibody responses compared to a single dose. In one-dose regimens neutralizing antibody responses were stable for at least 14 weeks, providing an early indication of durability. Ad26.COV2.S induced humoral immunity and Th1 skewed cellular responses in aged NHP that were comparable to adult animals. Importantly, aged Ad26.COV2.S-vaccinated animals challenged 3 months post -dose 1 with a SARS-CoV-2 spike G614 variant showed near complete lower and substantial upper respiratory tract protection for both regimens. These are the first NHP data showing COVID-19 vaccine protection against the SARS-CoV-2 spike G614 variant and support ongoing clinical Ad26.COV2.S development.SummaryCOVID-19 vaccines are urgently needed and while single-dose vaccines are preferred, two-dose regimens may improve efficacy. We show improved Ad26.COV2.S immunogenicity in non-human primates after a second vaccine dose, while both regimens protected aged animals against SARS-CoV-2 disease.

scholarly journals A chimeric dengue virus vaccine candidate delivered by high density microarray patches protects against infection in mice

npj Vaccines ◽  
2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Jovin J. Y. Choo ◽  
Laura J. Vet ◽  
Christopher L. D. McMillan ◽  
Jessica J. Harrison ◽  
Connor A. P. Scott ◽  
...  
Keyword(s):  
Virus Vaccine ◽  
Vaccine Candidate ◽  
Protective Efficacy ◽  
Neutralizing Antibody ◽  
High Density ◽  
E Proteins ◽  
Virus Challenge ◽  
Wide Range ◽  
Antibody Induction ◽  
Kinetics Of

AbstractDengue viruses (DENV) cause an estimated 390 million infections globally. With no dengue-specific therapeutic treatment currently available, vaccination is the most promising strategy for its control. A wide range of DENV vaccines are in development, with one having already been licensed, albeit with limited distribution. We investigated the immunogenicity and protective efficacy of a chimeric virus vaccine candidate based on the insect-specific flavivirus, Binjari virus (BinJV), displaying the structural prM/E proteins of DENV (BinJ/DENV2-prME). In this study, we immunized AG129 mice with BinJ/DENV2-prME via a needle-free, high-density microarray patch (HD-MAP) delivery system. Immunization with a single, 1 µg dose of BinJ/DENV2-prME delivered via the HD-MAPs resulted in enhanced kinetics of neutralizing antibody induction when compared to needle delivery and complete protection against mortality upon virus challenge in the AG129 DENV mouse model.

scholarly journals Efficacy of Coxsackievirus A5 Vaccine Candidates in an Actively Immunized Mouse Model

2021 ◽  
Author(s):  
Wei-Ping Jin ◽  
Jia Lu ◽  
Xiao-Yu Zhang ◽  
Jie Wu ◽  
Zhen-Ni Wei ◽  
...  
Keyword(s):  
Animal Model ◽  
Mouse Model ◽  
Neutralizing Antibodies ◽  
Large Scale ◽  
Vaccine Candidate ◽  
Protective Efficacy ◽  
Lethal Dose ◽  
Enterovirus 71 ◽  
Vaccine Candidates ◽  
Enterovirus Serotypes

Coxsackievirus A5 (CV-A5) has recently emerged as a main hand, foot and mouth disease (HFMD) pathogen. Following a large-scale vaccination campaign against enterovirus 71 (EV-71) in China, the number of HFMD-associated cases with EV-71 was reduced, especially severe and fatal cases. However, the total number of HFMD cases remains high, as HFMD is also caused by other enterovirus serotypes. A multivalent HFMD vaccine containing 4 or 6 antigens of enterovirus serotypes is urgently needed. A formaldehyde-inactivated CV-A5 vaccine derived from Vero cells was used to inoculate newborn Kunming mice on days 3 and 10. The mice were challenged on day 14 with a mouse-adapted CV-A5 strain at a lethal dose, which was lethal for 14-day-old suckling mice. Within 14 days post-challenge, groups of mice immunized with three formulations, empty particles (EPs), full particles (FPs) and a mixture of the EP and FP vaccine candidates, all survived, while 100% of the mock-immunized mice died. Neutralizing antibodies (NtAbs) were detected in the sera of immunized mice, and the NtAb levels were correlated with the survival rate of the challenged mice. The virus loads in organs were reduced, and pathological changes and viral protein expression were weak or not observed in the immunized mice compared with those in alum-inoculated control mice. Another interesting finding was the identification of CV-A5 dense particles (DPs), facilitating morphogenesis study. These results demonstrated that the Vero cell-adapted CV-A5 strain is a promising vaccine candidate and could be used as a multivalent HFMD vaccine component in the future. IMPORTANCE The vaccine candidate strain CV-A5 was produced with a high infectivity titer and a high viral particle yield. Three particle forms, empty particles (EPs), full particles (FPs) and dense particles (DPs), were obtained and characterized after purification. The immunogenicities of EP, FP, and EP+FP were evaluated in mice. Mouse-adapted CV-A5 was generated as a challenge strain to infect 14-day-old mice. An active immunization challenge mouse model was established to evaluate the efficacy of the inactivated vaccine candidate. This animal model mimics vaccination, similar immune responses of the vaccinated. The animal model also tests protective efficacy in response to the vaccine against the disease. This work is important for the preparation of multivalent vaccines against HFMD caused by different emerging strains.

scholarly journals SARS-CoV-2 Vaccines Elicit Durable Immune Responses in Infant Rhesus Macaques

2021 ◽  
Author(s):  
Carolina Garrido ◽  
Alan D. Curtis ◽  
Maria Dennis ◽  
Sachi H. Pathak ◽  
Hongmei Gao ◽  
...  
Keyword(s):  
Immune Responses ◽  
Protective Immunity ◽  
Rhesus Macaques ◽  
Herd Immunity ◽  
Cellular Responses ◽  
Infectious Dose ◽  
Vaccine Candidates ◽  
Cell Responses ◽  
High Magnitude ◽  
Infant Rhesus

AbstractEarly life SARS-CoV-2 vaccination has the potential to provide lifelong protection and achieve herd immunity. To evaluate SARS-CoV-2 infant vaccination, we immunized two groups of 8 infant rhesus macaques (RMs) at weeks 0 and 4 with stabilized prefusion SARS-CoV-2 S-2P spike (S) protein, either encoded by mRNA encapsulated in lipid nanoparticles (mRNA-LNP) or mixed with 3M-052-SE, a TLR7/8 agonist in a squalene emulsion (Protein+3M-052-SE). Neither vaccine induced adverse effects. High magnitude S-binding IgG and neutralizing infectious dose 50 (ID50) >103 were elicited by both vaccines. S-specific T cell responses were dominated by IL-17, IFN-γ, or TNF-α. Antibody and cellular responses were stable through week 22. The S-2P mRNA-LNP and Protein-3M-052-SE vaccines are promising pediatric SARS-CoV-2 vaccine candidates to achieve durable protective immunity.One-Sentence SummarySARS-CoV-2 vaccines are well-tolerated and highly immunogenic in infant rhesus macaques

scholarly journals Safety, immunogenicity, and protection provided by unadjuvanted and adjuvanted formulations of a recombinant plant-derived virus-like particle vaccine candidate for COVID-19 in nonhuman primates

2022 ◽  
Author(s):  
Stéphane Pillet ◽  
Prabhu S. Arunachalam ◽  
Guadalupe Andreani ◽  
Nadia Golden ◽  
Jane Fontenot ◽  
...  
Keyword(s):  
Immune Cell ◽  
Vaccine Development ◽  
Vaccine Candidate ◽  
Rhesus Macaques ◽  
Interleukin 2 ◽  
Lavage Fluid ◽  
Booster Immunization ◽  
Recombinant Plant ◽  
Virus Like Particle ◽  
Multiple Routes

AbstractAlthough antivirals are important tools to control severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, effective vaccines are essential to control the current coronavirus disease 2019 (COVID-19) pandemic. Plant-derived virus-like particle (VLP) vaccine candidates have previously demonstrated immunogenicity and efficacy against influenza. Here, we report the immunogenicity and protection induced in rhesus macaques by intramuscular injections of a VLP bearing a SARS-CoV-2 spike protein (CoVLP) vaccine candidate formulated with or without Adjuvant System 03 (AS03) or cytidine-phospho-guanosine (CpG) 1018. Although a single dose of the unadjuvanted CoVLP vaccine candidate stimulated humoral and cell-mediated immune responses, booster immunization (at 28 days after priming) and adjuvant administration significantly improved both responses, with higher immunogenicity and protection provided by the AS03-adjuvanted CoVLP. Fifteen micrograms of CoVLP adjuvanted with AS03 induced a polyfunctional interleukin-2 (IL-2)-driven response and IL-4 expression in CD4 T cells. Animals were challenged by multiple routes (i.e., intratracheal, intranasal, and ocular) with a total viral dose of 106 plaque-forming units of SARS-CoV-2. Lower viral replication in nasal swabs and bronchoalveolar lavage fluid (BALF) as well as fewer SARS-CoV-2-infected cells and immune cell infiltrates in the lungs concomitant with reduced levels of proinflammatory cytokines and chemotactic factors in the BALF were observed in animals immunized with the CoVLP adjuvanted with AS03. No clinical, pathologic, or virologic evidence of vaccine-associated enhanced disease was observed in vaccinated animals. The CoVLP adjuvanted with AS03 was therefore selected for vaccine development and clinical trials.

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