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

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

doi:10.1016/j.isci.2021.102298

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

iScience. 2021 Apr 23;24(4):102298. doi: 10.1016/j.isci.2021.102298. Epub 2021 Mar 10.

Authors

Brunda Ganneru¹, Harsh Jogdand¹, Vijaya Kumar Daram¹, Dipankar Das¹, Narasimha Reddy Molugu¹, Sai D Prasad¹, Srinivas V Kannappa¹, Krishna M Ella¹, Rajaram Ravikrishnan², Amit Awasthi³, Jomy Jose², Panduranga Rao¹, Deepak Kumar¹, Raches Ella¹, Priya Abraham⁴, Pragya D Yadav⁴, Gajanan N Sapkal⁴, Anita Shete-Aich⁴, Gururaj Desphande⁴, Sreelekshmy Mohandas⁴, Atanu Basu⁴, Nivedita Gupta⁵, Krishna Mohan Vadrevu¹

Affiliations

¹ Bharat Biotech International Ltd, Hyderabad (BBIL), Telangana 500 078, India.
² RCC Laboratories India Private Ltd, Hyderabad, Telangana 500 078, India.
³ Translational Health Sciences and Technology Institute (THSTI), NCR Biotech Science Cluster, PO box #04, Faridabad, Haryana 121001, India.
⁴ National Institute of Virology-Indian Council of Medical Research (NIV-ICMR), Pune, Maharashtra 411021, India.
⁵ Indian Council of Medical Research (ICMR), India, V. Ramalingaswami Bhawan, P.O. Box No. 4911, Ansari Nagar, New Delhi 110029, India.

Abstract

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.

Keywords: Immune Response; Immunology; Virology.