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.
| Originalsprog | Engelsk |
|---|---|
| Artikelnummer | 105949 |
| Tidsskrift | iScience |
| Vol/bind | 26 |
| Udgave nummer | 2 |
| ISSN | 2589-0042 |
| DOI | |
| Status | Udgivet - 2023 |
Bibliografisk note
Funding Information:We thank Lotte Mikkelsen, Anna-Louise Sørensen, and Pia Pedersen (Copenhagen University Hospital–Hvidovre), as well as Julia Sid Hansen and Rune Fledelius Jensen (Statens Serum Institut) for laboratory assistance and Bjarne Ø. Lindhardt (Copenhagen University Hospital–Hvidovre) and Charlotte M. Bonefeld (University of Copenhagen) for their support. We thank Qing Wang and Svenja Schulz for technical assistance (Max Planck Institute for Dynamics of Complex Technical Systems), Rachel Mellwig for transmission electron microscopy pictures (EMBL Heidelberg), and Yvonne Genzel and Udo Reichl for discussion and support (Max Planck Institute for Dynamics of Complex Technical Systems). We thank Esco Aster Pte Ltd. (Singapore) for making a CelCradle bioreactor available and Jean Dubuisson (University of Lille) for providing VeroE6 cells. We acknowledge funding from the Candys Foundation , the Danish Agency for Science and Higher Education , the European Social Fund (ESF) , the German Federal Ministry for Economic Affairs and Energy (BMWi), the Hvidovre Hospital Research Foundation , the Independent Research Fund Denmark , the Innovation Fund Denmark , the Læge Sophus Carl Emil Friis og hustru Olga Doris Friis’ Legat , the Mauritzen La Fontaine (MLF) Fonden, the Max Planck Society (MPG), and the Toyota Foundation .
Funding Information:
We thank Lotte Mikkelsen, Anna-Louise Sørensen, and Pia Pedersen (Copenhagen University Hospital–Hvidovre), as well as Julia Sid Hansen and Rune Fledelius Jensen (Statens Serum Institut) for laboratory assistance and Bjarne Ø. Lindhardt (Copenhagen University Hospital–Hvidovre) and Charlotte M. Bonefeld (University of Copenhagen) for their support. We thank Qing Wang and Svenja Schulz for technical assistance (Max Planck Institute for Dynamics of Complex Technical Systems), Rachel Mellwig for transmission electron microscopy pictures (EMBL Heidelberg), and Yvonne Genzel and Udo Reichl for discussion and support (Max Planck Institute for Dynamics of Complex Technical Systems). We thank Esco Aster Pte Ltd. (Singapore) for making a CelCradle bioreactor available and Jean Dubuisson (University of Lille) for providing VeroE6 cells. We acknowledge funding from the Candys Foundation, the Danish Agency for Science and Higher Education, the European Social Fund (ESF), the German Federal Ministry for Economic Affairs and Energy (BMWi), the Hvidovre Hospital Research Foundation, the Independent Research Fund Denmark, the Innovation Fund Denmark, the Læge Sophus Carl Emil Friis og hustru Olga Doris Friis’ Legat, the Mauritzen La Fontaine (MLF) Fonden, the Max Planck Society (MPG), and the Toyota Foundation. Conceptualization, A.O. and J.M.G.; formal analysis, A.O. C.R.D.H. S.F. P.M-G. K.H. A.F.P. C.F-A. K.T.H. U.F. U.V.S. G.K.P. H.E.J. J.P.C. and J.M.G.; funding acquisition, P.M-G. J.B. and J.M.G.; investigation, A.O. C.R.D.H. S.F. P.M-G. K.H. A.F.P. C.F-A. G.P.A. K.T.H. L.V.P. Y.Z. K.A.G. U.V.S. G.K.P. H.E.J. and J.P.C.; methodology, A.O. S.F. P.M-G. K.H. C.F-A. L.V.P. U.F. G.K.P. S.R. and J.M.G.; supervision, J.B. and J.M.G.; writing – original draft, A.O. and J.M.G.; writing – review and editing, all authors reviewed the manuscript. A.O. C.R.D.H. S.F. K.H. A.F.P. C.F-A. G.P.A. K.T.H. L.V.P. Y.Z. K.A.G. U.F. U.V.S. G.K.P. H.E.J. J.P.C. S.R. J.B. and J.M.G. declare no conflict of interests. P.M-G. is an inventor in pending patent applications related to the SXC purification method described in this work.
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