iScience (Feb 2023)
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
Affiliations
- Anna Offersgaard
- Copenhagen Hepatitis C Program (CO-HEP), Department of Infectious Diseases, Copenhagen University Hospital–Hvidovre, 2650 Hvidovre, Denmark; CO-HEP, Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen N, Denmark
- Carlos Rene Duarte Hernandez
- Copenhagen Hepatitis C Program (CO-HEP), Department of Infectious Diseases, Copenhagen University Hospital–Hvidovre, 2650 Hvidovre, Denmark; CO-HEP, Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen N, Denmark
- Shan Feng
- Copenhagen Hepatitis C Program (CO-HEP), Department of Infectious Diseases, Copenhagen University Hospital–Hvidovre, 2650 Hvidovre, Denmark; CO-HEP, Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen N, Denmark
- Pavel Marichal-Gallardo
- Bioprocess Engineering, Max Planck Institute for Dynamics of Complex Technical Systems, 39106 Magdeburg, Germany
- Kenn Holmbeck
- Copenhagen Hepatitis C Program (CO-HEP), Department of Infectious Diseases, Copenhagen University Hospital–Hvidovre, 2650 Hvidovre, Denmark; CO-HEP, Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen N, Denmark
- Anne Finne Pihl
- Copenhagen Hepatitis C Program (CO-HEP), Department of Infectious Diseases, Copenhagen University Hospital–Hvidovre, 2650 Hvidovre, Denmark; CO-HEP, Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen N, Denmark
- Carlota Fernandez-Antunez
- Copenhagen Hepatitis C Program (CO-HEP), Department of Infectious Diseases, Copenhagen University Hospital–Hvidovre, 2650 Hvidovre, Denmark; CO-HEP, Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen N, Denmark
- Garazi Peña Alzua
- Copenhagen Hepatitis C Program (CO-HEP), Department of Infectious Diseases, Copenhagen University Hospital–Hvidovre, 2650 Hvidovre, Denmark; CO-HEP, Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen N, Denmark
- Katrine Top Hartmann
- Department of Veterinary and Animal Sciences, University of Copenhagen, 1870 Frederiksberg C, Denmark
- Long V. Pham
- Copenhagen Hepatitis C Program (CO-HEP), Department of Infectious Diseases, Copenhagen University Hospital–Hvidovre, 2650 Hvidovre, Denmark; CO-HEP, Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen N, Denmark
- Yuyong Zhou
- Copenhagen Hepatitis C Program (CO-HEP), Department of Infectious Diseases, Copenhagen University Hospital–Hvidovre, 2650 Hvidovre, Denmark; CO-HEP, Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen N, Denmark
- Karen Anbro Gammeltoft
- Copenhagen Hepatitis C Program (CO-HEP), Department of Infectious Diseases, Copenhagen University Hospital–Hvidovre, 2650 Hvidovre, Denmark; CO-HEP, Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen N, Denmark
- Ulrik Fahnøe
- Copenhagen Hepatitis C Program (CO-HEP), Department of Infectious Diseases, Copenhagen University Hospital–Hvidovre, 2650 Hvidovre, Denmark; CO-HEP, Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen N, Denmark
- Uffe Vest Schneider
- Department of Clinical Microbiology, Copenhagen University Hospital–Hvidovre, 2650 Hvidovre, Denmark
- Gabriel Kristian Pedersen
- Center for Vaccine Research, Statens Serum Institut, 2300 Copenhagen S, Denmark
- Henrik Elvang Jensen
- Department of Veterinary and Animal Sciences, University of Copenhagen, 1870 Frederiksberg C, Denmark
- Jan Pravsgaard Christensen
- Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen N, Denmark
- Santseharay Ramirez
- Copenhagen Hepatitis C Program (CO-HEP), Department of Infectious Diseases, Copenhagen University Hospital–Hvidovre, 2650 Hvidovre, Denmark; CO-HEP, Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen N, Denmark
- Jens Bukh
- Copenhagen Hepatitis C Program (CO-HEP), Department of Infectious Diseases, Copenhagen University Hospital–Hvidovre, 2650 Hvidovre, Denmark; CO-HEP, Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen N, Denmark
- Judith Margarete Gottwein
- Copenhagen Hepatitis C Program (CO-HEP), Department of Infectious Diseases, Copenhagen University Hospital–Hvidovre, 2650 Hvidovre, Denmark; CO-HEP, Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen N, Denmark; Corresponding author
- Journal volume & issue
-
Vol. 26,
no. 2
p. 105949
Abstract
Summary: 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.
