Th1 skewed immune response of whole virion inactivated SARS CoV 2 vaccine and its safety evaluation

• Main Authors: Brunda Ganneru, Harsh Jogdand, Vijaya Kumar Daram, Dipankar Das, Narasimha Reddy Molugu, Sai D. Prasad, Srinivas V. Kannappa, Krishna M. Ella, Rajaram Ravikrishnan, Amit Awasthi, Jomy Jose, Panduranga Rao, Deepak Kumar, Raches Ella, Priya Abraham, Pragya D. Yadav, Gajanan N. Sapkal, Anita Shete-Aich, Gururaj Desphande, Sreelekshmy Mohandas, Atanu Basu, Nivedita Gupta, Krishna Mohan Vadrevu
• Format: Article
• Language: English
• Published: Elsevier 2021-04-01
• Series: iScience
• Subjects: Immune Response; Immunology; Virology
• Online Access: http://www.sciencedirect.com/science/article/pii/S2589004221002662

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.