Summary We report the development and evaluation of safety and immunogenicity of a whole virion inactivated (WVI) SARS-CoV-2 vaccine (BBV152), adjuvanted with aluminum hydroxide gel (Algel), or TLR7/8 agonist chemisorbed 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. Product development and manufacturing process were carried out in a BSL-3 facility. Immunogenicity and safety were 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 (NAb), at both concentrations, in all three species with excellent safety profiles. The inactivated vaccine formulation contains 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. Graphical abstract Highlights • WVI SARS-CoV-2 vaccine (BBV152) was developed using genetically stable strain • Adjuvanted vaccines (BBV152A, B, and C) induced high NAb titers in animal models • Chemisorbed Algel with TLR7/8 agonists vaccine formulations (BBV152A & B) induced robust Th1 biased immunity • Adjuvanted vaccines (BBV152A, B, and C) are found to be safe in animal models Immune Response ; Microbiology ; Virology
【저자키워드】 immunology, immune response, Virology, 【초록키워드】 Vaccine, immunogenicity, clinical trial, Microbiology, Immunity, Antibody Response, Th1, animal model, adjuvants, CD4, SARS-CoV-2 vaccine, Antigen, Inactivated vaccine, mice, humans, response, platform, inactivated, IFN-γ, Neutralizing antibody titer, Concentration, aluminum, Safe, Support, Abstract, profiles, hydroxide, product, TLR7/8, agonist, virion, SARS-CoV-2 strain, Vero Cell, concentrations, NAb titer, robust, BSL-3 facility, carried, significantly, elevated, purified, gel, T lymphocyte response, 【제목키워드】 Vaccine, Th1, inactivated, SARS CoV, virion, skewed,