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

Anna Offersgaard; Carlos Rene Duarte Hernandez; Shan Feng; Pavel Marichal-Gallardo; Kenn Holmbeck; Anne Finne Pihl; Carlota Fernandez-Antunez; Garazi Peña Alzua; Katrine Top Hartmann; Long V Pham; Yuyong Zhou; Karen Anbro Gammeltoft; Ulrik Fahnøe; Uffe Vest Schneider; Gabriel Kristian Pedersen; Henrik Elvang Jensen; Jan Pravsgaard Christensen; Santseharay Ramirez; Jens Bukh; Judith Margarete Gottwein

doi:10.1016/j.isci.2023.105949

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

iScience. 2023 Feb 17;26(2):105949. doi: 10.1016/j.isci.2023.105949. Epub 2023 Jan 10.

Authors

Anna Offersgaard^{1

2}, Carlos Rene Duarte Hernandez^{1

2}, Shan Feng^{1

2}, Pavel Marichal-Gallardo³, Kenn Holmbeck^{1

2}, Anne Finne Pihl^{1

2}, Carlota Fernandez-Antunez^{1

2}, Garazi Peña Alzua^{1

2}, Katrine Top Hartmann⁴, Long V Pham^{1

2}, Yuyong Zhou^{1

2}, Karen Anbro Gammeltoft^{1

2}, Ulrik Fahnøe^{1

2}, Uffe Vest Schneider⁵, Gabriel Kristian Pedersen⁶, Henrik Elvang Jensen⁴, Jan Pravsgaard Christensen⁷, Santseharay Ramirez^{1

2}, Jens Bukh^{1

2}, Judith Margarete Gottwein^{1

2}

Affiliations

¹ Copenhagen Hepatitis C Program (CO-HEP), Department of Infectious Diseases, Copenhagen University Hospital-Hvidovre, 2650 Hvidovre, Denmark.
² CO-HEP, Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen N, Denmark.
³ Bioprocess Engineering, Max Planck Institute for Dynamics of Complex Technical Systems, 39106 Magdeburg, Germany.
⁴ Department of Veterinary and Animal Sciences, University of Copenhagen, 1870 Frederiksberg C, Denmark.
⁵ Department of Clinical Microbiology, Copenhagen University Hospital-Hvidovre, 2650 Hvidovre, Denmark.
⁶ Center for Vaccine Research, Statens Serum Institut, 2300 Copenhagen S, Denmark.
⁷ Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen N, Denmark.

Abstract

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.

Keywords: Immune response; Immunology; Virology.