Evaluation of Safety and Immunogenicity of an Adjuvanted, TH-1 Skewed, Whole Virion InactivatedSARS-CoV-2 Vaccine - BBV152

Abstract

We report the development and evaluation of safety and immunogenicity of a whole virion inactivated SARS-COV-2 vaccine (BBV152), adjuvanted with aluminium hydroxide gel (Algel), or a novel TLR7/8 agonist adsorbed Algel. We used a well-characterized SARS-CoV-2 strain and an established vero cell platform to produce large-scale GMP grade highly purified inactivated antigen, BBV152. Product development and manufacturing were carried out in a BSL-3 facility. Immunogenicity was determined at two antigen concentrations (3μg and 6μg), with two different adjuvants, in mice, rats, and rabbits. Our results show that BBV152 vaccine formulations generated significantly high antigen-binding and neutralizing antibody titers, at both concentrations, in all three species with excellent safety profiles. The inactivated vaccine formulation containing TLR7/8 agonist adjuvant-induced Th1 biased antibody responses with elevated IgG2a/IgG1 ratio and increased levels of SARS-CoV-2 specific IFN-γ+ CD4 T lymphocyte response. Our results support further development for Phase I/II clinical trials in humans.

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

“…Preclinical studies on BBV152 adjuvanted with this molecule reported a Th1-biased response in mice. 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 …”

“…Preclinical studies in mice, rats, and rabbits showed appropriate safety profiles and humoral and cell-mediated responses. 7 Two live viral challenge protective efficacy studies in hamsters and non-human primates were done. 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).…”

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

“…G clade sequences are predominantly circulating in India and contribute to~74% of the SARS-CoV-2 sequences circulating in the world [26][27][28] . The genetic stability of the NIV-2020-770 strain was demonstrated by multiple passages in Vero CCL-81 cells and by next-generation sequencing 7 . Virus propagation was done in a bioreactor (Corning Life Science) at the temperature of 36 ± 1°C and was harvested at 36-72 h post infection and supernatants were collected, clarified and aliquoted.…”

“…The safety and the immunogenicity of inactivated vaccine candidate BBV152 has been established in mice, rat and rabbit models 7 .The vaccine candidate has been found to induce an effective humoral immune response and protects Syrian hamsters from SARS-CoV-2 pneumonia 8 . Here, we report the assessment of immunogenicity and protective efficacy of three formulations of a purified whole-virion-inactivated SARS-CoV-2 vaccine candidate BBV152 in the rhesus macaques.…”

SARS-CoV-2: Targeted managements and vaccine development

“…Covaxin (BBV152) (3 or 6 µg) injected with aluminum hydroxide gel or a TLR7/8 agonist absorbed gel as adjuvant demonstrated good immunogenicity in mice, rats, and rabbits [ 137 ]. The injection of Covaxin (3 µg) and TLR7/8 agonist absorbed gel in a 2-doses vaccination scheduled 14 days apart provides an immune protection to macaques when challenged by SARS-CoV-2 [ 138 ].…”