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Trimeric SARS-CoV-2 Spike Proteins Produced from CHO Cells in Bioreactors Are High-Quality Antigens

ExcellGene SA, CH1870 Monthey, Switzerland
Department of Immunology and Allergy, Centre Hospitalier Universitaire Vaudois, (CHUV), 1011 Lausanne, Switzerland
Centre de Recherche en Biologie cellulaire de Montpellier, Université Montpellier, 34293 Montpellier, France
Unit Peptide and Protein Chemistry and Biology, Department of NeuroFarBra, University of Florence, 50019 Sesto Florentino, Italy
Institute for Infectious Diseases, University of Bern, 3001 Bern, Switzerland
Institute of Virology and Immunology (IVI), 3012 Bern, Switzerland
Department of Infectious Diseases and Pathobiology, Vetsuisse Faculty, University of Bern, 3012 Bern, Switzerland
Department of Immuno-Surveillance, Centre for Immunology of Infectious Diseases and Vaccines, National Institute for Public Health and the Environment, 3741MA Bilthoven, The Netherlands
Department of Molecular Biosciences, University of Texas at Austin, Austin, TX 78712, USA
Life Science Faculty, Swiss Federal Institute of Technology Lausanne (EPFL), 1015 Lausanne, Switzerland
Authors to whom correspondence should be addressed.
Processes 2020, 8(12), 1539;
Received: 8 November 2020 / Revised: 23 November 2020 / Accepted: 24 November 2020 / Published: 25 November 2020
(This article belongs to the Special Issue Redesign Processes in the Age of the Fourth Industrial Revolution)
The spike protein of the pandemic human corona virus is essential for its entry into human cells. In fact, most neutralizing antibodies against Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2) are directed against the Virus-surface exposed spike protein, making it the antigen of choice for use in vaccines and diagnostic tests. In the current pandemic context, global demand for spike proteins has rapidly increased and could exceed hundreds of grams to kilograms annually. Coronavirus spikes are large heavily glycosylated homo-trimeric complexes, with inherent instability. The poor manufacturability now threatens the availability of these proteins for vaccines and diagnostic tests. Here, we outline scalable, Good Manufacturing Practice (GMP) compliant, and chemically defined processes for the production of two cell-secreted stabilized forms of the trimeric spike proteins (Wuhan and D614G variant). The processes are chemically defined and based on clonal suspension-CHO cell populations and on protein purification via a two-step scalable downstream process. The trimeric conformation was confirmed using electron microscopy and HPLC analysis. Binding to susceptible cells was shown using a virus-inhibition assay. The diagnostic sensitivity and specificity for detection of serum SARS-CoV-2-specific-immunoglobulin molecules was found to exceed that of spike fragments (Spike subunit-1, S1 and Receptor Binding Domain, RBD). The process described here will enable production of sufficient high-quality trimeric spike protein to meet the global demand for SARS-CoV-2 diagnostic tests and potentially vaccines. View Full-Text
Keywords: SARS-CoV-2; trimeric spike; CHO cells; manufacturability; vaccines; diagnostics SARS-CoV-2; trimeric spike; CHO cells; manufacturability; vaccines; diagnostics
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MDPI and ACS Style

Pino, P.; Kint, J.; Kiseljak, D.; Agnolon, V.; Corradin, G.; Kajava, A.V.; Rovero, P.; Dijkman, R.; den Hartog, G.; McLellan, J.S.; Byrne, P.O.; Wurm, M.J.; Wurm, F.M. Trimeric SARS-CoV-2 Spike Proteins Produced from CHO Cells in Bioreactors Are High-Quality Antigens. Processes 2020, 8, 1539.

AMA Style

Pino P, Kint J, Kiseljak D, Agnolon V, Corradin G, Kajava AV, Rovero P, Dijkman R, den Hartog G, McLellan JS, Byrne PO, Wurm MJ, Wurm FM. Trimeric SARS-CoV-2 Spike Proteins Produced from CHO Cells in Bioreactors Are High-Quality Antigens. Processes. 2020; 8(12):1539.

Chicago/Turabian Style

Pino, Paco, Joeri Kint, Divor Kiseljak, Valentina Agnolon, Giampietro Corradin, Andrey V. Kajava, Paolo Rovero, Ronald Dijkman, Gerco den Hartog, Jason S. McLellan, Patrick O. Byrne, Maria J. Wurm, and Florian M. Wurm 2020. "Trimeric SARS-CoV-2 Spike Proteins Produced from CHO Cells in Bioreactors Are High-Quality Antigens" Processes 8, no. 12: 1539.

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