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

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 devel...

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Main Authors: 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
Format: Article
Language:English
Published: Elsevier 2023-02-01
Series:iScience
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2589004223000263
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author 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
author_facet 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
author_sort Anna Offersgaard
collection DOAJ
description 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.
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spelling doaj.art-5be313e70944483e85a0601f5bf5dfe32023-02-19T04:26:41ZengElsevieriScience2589-00422023-02-01262105949An inactivated SARS-CoV-2 vaccine induced cross-neutralizing persisting antibodies and protected against challenge in small animalsAnna Offersgaard0Carlos Rene Duarte Hernandez1Shan Feng2Pavel Marichal-Gallardo3Kenn Holmbeck4Anne Finne Pihl5Carlota Fernandez-Antunez6Garazi Peña Alzua7Katrine Top Hartmann8Long V. Pham9Yuyong Zhou10Karen Anbro Gammeltoft11Ulrik Fahnøe12Uffe Vest Schneider13Gabriel Kristian Pedersen14Henrik Elvang Jensen15Jan Pravsgaard Christensen16Santseharay Ramirez17Jens Bukh18Judith Margarete Gottwein19Copenhagen 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, DenmarkCopenhagen 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, DenmarkCopenhagen 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, DenmarkBioprocess Engineering, Max Planck Institute for Dynamics of Complex Technical Systems, 39106 Magdeburg, GermanyCopenhagen 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, DenmarkCopenhagen 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, DenmarkCopenhagen 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, DenmarkCopenhagen 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, DenmarkDepartment of Veterinary and Animal Sciences, University of Copenhagen, 1870 Frederiksberg C, DenmarkCopenhagen 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, DenmarkCopenhagen 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, DenmarkCopenhagen 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, DenmarkCopenhagen 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, DenmarkDepartment of Clinical Microbiology, Copenhagen University Hospital–Hvidovre, 2650 Hvidovre, DenmarkCenter for Vaccine Research, Statens Serum Institut, 2300 Copenhagen S, DenmarkDepartment of Veterinary and Animal Sciences, University of Copenhagen, 1870 Frederiksberg C, DenmarkDepartment of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen N, DenmarkCopenhagen 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, DenmarkCopenhagen 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, DenmarkCopenhagen 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 authorSummary: 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.http://www.sciencedirect.com/science/article/pii/S2589004223000263ImmunologyImmune responseVirology
spellingShingle 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
An inactivated SARS-CoV-2 vaccine induced cross-neutralizing persisting antibodies and protected against challenge in small animals
iScience
Immunology
Immune response
Virology
title An inactivated SARS-CoV-2 vaccine induced cross-neutralizing persisting antibodies and protected against challenge in small animals
title_full An inactivated SARS-CoV-2 vaccine induced cross-neutralizing persisting antibodies and protected against challenge in small animals
title_fullStr An inactivated SARS-CoV-2 vaccine induced cross-neutralizing persisting antibodies and protected against challenge in small animals
title_full_unstemmed An inactivated SARS-CoV-2 vaccine induced cross-neutralizing persisting antibodies and protected against challenge in small animals
title_short An inactivated SARS-CoV-2 vaccine induced cross-neutralizing persisting antibodies and protected against challenge in small animals
title_sort inactivated sars cov 2 vaccine induced cross neutralizing persisting antibodies and protected against challenge in small animals
topic Immunology
Immune response
Virology
url http://www.sciencedirect.com/science/article/pii/S2589004223000263
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