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

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).

Immunogenicity and protective efficacy of BBV152, whole virion inactivated SARS- CoV-2 vaccine candidates in the Syrian hamster model

“…SARS-CoV-2 vaccination experiments in hamster and rhesus macaque models also indicated the same ( Tostanoski et al., 2020 ; Yu et al., 2020 ). BBV152 induced SARS-CoV-2-specific IgG or NAbs in hamsters from third week post-immunization similar to the response observed in mice, rats, rabbits, and rhesus macaques ( Ganneru et al., 2020 ; Yadav et al., 2020 ). In other SARS-CoV-2 inactivated vaccine candidates like PiCoVacc and BBIBP-CorV, studied in non-human primate model, the NAb were observed from first and second week, respectively, with a period of detection till 5 weeks ( Gao et al., 2020 ; Wang et al., 2020 ).…”

Safety and immunogenicity of an inactivated SARS-CoV-2 vaccine, BBV152: a double-blind, randomised, phase 1 trial

“… 7 Furthermore, in a non-human primate and hamster live viral challenge studies, Algel-IMDG formulations led to higher neutralising antibodies, which might have resulted in improved upper and lower airway viral clearance (after challenge). 8 , 9 …”

“…In both studies, protection was evident by rapid clearance of virus in the lower and upper respiratory tract, and absence of lung pathology (after viral challenge). 8 , 9 Here, we report the interim findings from the randomised, controlled, double-blind phase 1 trial on the safety and immunogenicity of three different formulations of BBV152 and one control group containing Algel (without antigen). This phase 1 trial was done with the intention of selecting two formulations for progression to the phase 2 trial.…”

Development of SARS-CoV-2 vaccines: challenges, risks, and the way forward

“…83 Seven NHP trials of the candidate SARS-CoV-2 vaccines in the macaque challenge model have been published so far. [84][85][86][87][88][89][90] They include three adjuvanted inactivated vaccines (PiCoVacc by Sinovac, BBIBP-CorV, and BBV152 by BBIL), two nonreplicating adenovirus vector vaccines (ChAdOx1nCOV-19 by AstraZeneca and Ad26COVS1 by Janssen), one mRNA vaccine (mRNA-1273 by Moderna), and one protein subunit, nanoparticle vaccine (NVX CoV2373 by Novavax) [84][85][86][87][88][89][90] .…”