An inactivated SARS-CoV-2 vaccine induced cross-neutralizing persisting antibodies and protected against challenge in small animals

• DOI: 10.1016/j.isci.2023.105949
• Publication Date: 2023-01-10T01:50:54Z
• Authors: Anna Offersgaard; Carlos Rene Duart...; Shan Feng; Pavel Marichal-Ga...; Kenn Holmbeck; Anne Finne Pihl; Carlota Fernandez...; Garazi Peña Alzua; Katrine Top Hartmann; Long V. Pham; Yuyong Zhou; Karen Anbro Gamme...; Ulrik Fahnøe; Uffe Vest Schneider; Gabriel Kristian ...; Henrik Elvang Jensen; Jan Pravsgaard Ch...; Santseharay Ramirez; Jens Bukh; Judith Margarete ...
• Keywords: 0301 basic medicine; 0303 health sciences; 03 medical and health sciences; Virology; Science; Immunology; Q; Immune response; Article; 3. Good health

Vaccines have relieved the public health burden of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and globally inactivated vaccines are most widely used. However, poor vaccination accessibility and waning immunity maintain the pandemic, driving emergence of variants. We developed an inactivated SARS-CoV-2 (I-SARS-CoV-2) vaccine based on a viral isolate with the Spike mutation D614G, produced in Vero cells in a scalable bioreactor, inactivated with β-propiolactone, purified by membrane-based steric exclusion chromatography, and adjuvanted with MF59-like adjuvant AddaVax. I-SARS-CoV-2 and a derived split vaccine induced persisting neutralizing antibodies in mice; moreover, lyophilized antigen was immunogenic. Following homologous challenge, I-SARS-CoV-2 immunized hamsters were protected against disease and lung pathology. In contrast with reports for widely used vaccines, hamster plasma similarly neutralized the homologous and the Delta (B.1.617.2) variant viruses, whereas the Omicron (B.1.1.529) variant was neutralized less efficiently. Applied bioprocessing approaches offer advantages regarding scalability and production, potentially benefitting worldwide vaccine coverage.