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A SARS-CoV-2 Neutralizing Antibody Selected from COVID-19 Patients by Phage Display is Binding to the ACE2-RBD Interface and is Tolerant to Known RBD Mutations

67 Pages Posted: 23 Dec 2020 Publication Status: Under Review

See all articles by Federico Bertoglio

Federico Bertoglio

Technology University of Braunschweig - Institut für Biochemie, Biotechnologie und Bioinformatik

Viola Fühner

Technology University of Braunschweig - Institut für Biochemie, Biotechnologie und Bioinformatik

Maximilian Ruschig

Technology University of Braunschweig - Institut für Biochemie, Biotechnologie und Bioinformatik

Philip Alexander Heine

Technology University of Braunschweig - Institut für Biochemie, Biotechnologie und Bioinformatik

Ulfert Rand

Helmholtz Centre for Infection Research - Department of Vaccinology and Applied Microbiology

Thomas Klünemann

Helmholtz Centre for Infection Research - Department of Structure and Function of Proteins

Doris Meier

Technology University of Braunschweig - Institut für Biochemie, Biotechnologie und Bioinformatik

Nora Langreder

Technology University of Braunschweig - Institut für Biochemie, Biotechnologie und Bioinformatik

Stephan Steinke

Technology University of Braunschweig - Institut für Biochemie, Biotechnologie und Bioinformatik

Rico Ballmann

Technology University of Braunschweig - Institut für Biochemie, Biotechnologie und Bioinformatik

Kai-Thomas Schneider

Technology University of Braunschweig - Institut für Biochemie, Biotechnologie und Bioinformatik

Kristian Danial Ralph Roth

Technology University of Braunschweig - Institut für Biochemie, Biotechnologie und Bioinformatik

Philipp Kuhn

YUMAB GmbH

Peggy Riese

Helmholtz Centre for Infection Research - Department of Vaccinology and Applied Microbiology

Dorina Schäckermann

Technology University of Braunschweig - Institut für Biochemie, Biotechnologie und Bioinformatik

Janin Korn

Technology University of Braunschweig - Institut für Biochemie, Biotechnologie und Bioinformatik

Allan Koch

Technology University of Braunschweig - Institut für Biochemie, Biotechnologie und Bioinformatik

Susanne Zock-Emmenthal

Technology University of Braunschweig - Institut für Genetik

Marlies Becker

Technology University of Braunschweig - Institut für Biochemie, Biotechnologie und Bioinformatik

Margitta Scholz

Technology University of Braunschweig - Institut für Biochemie, Biotechnologie und Bioinformatik

Gustavo Marçal Schmidt Garcia Moreira

Technology University of Braunschweig - Institut für Biochemie, Biotechnologie und Bioinformatik

Esther Veronika Wenzel

Technology University of Braunschweig - Institut für Biochemie, Biotechnologie und Bioinformatik

Giulio Russo

Technology University of Braunschweig - Institut für Biochemie, Biotechnologie und Bioinformatik

Hendrikus S.P. Garritsen

Städtisches Klinikum Braunschweig gGmbH

Sebastian Casu

Helios Klinikum Salzgitter

Andreas Gerstner

Städtisches Klinikum Braunschweig gGmbH

Günter Roth

BioCopy GmbH

Andreas Hermann

CORAT Therapeutics GmbH

Thomas Schirrmann

YUMAB GmbH

Stefan Dübel

Technology University of Braunschweig - Institut für Biochemie, Biotechnologie und Bioinformatik

André Frenzel

YUMAB GmbH

Joop Van den Heuvel

Helmholtz Centre for Infection Research - Department of Structure and Function of Proteins

Luka Cicin-Sain

Helmholtz Centre for Infection Research - Department of Vaccinology

Maren Schubert

Technology University of Braunschweig - Institut für Biochemie, Biotechnologie und Bioinformatik

Michael Hust

Technology University of Braunschweig - Institut für Biochemie, Biotechnologie und Bioinformatik

More...

Abstract

The novel betacoranavirus SARS-CoV-2 causes a form of severe pneumonia disease, termed COVID-19 (coronavirus disease 2019). Recombinant human antibodies are proven potent neutralizers of viruses and can block the interaction of viral surface proteins with their host receptors. To develop neutralizing anti-SARS-CoV-2 antibodies, antibody gene libraries from convalescent COVID-19 patients were constructed and recombinant antibody fragments (scFv) against the receptor binding domain (RBD) of the S1 subunit of the viral spike (S) protein were selected by phage display. The selected antibodies were produced in the scFv-Fc format and 30 showed more than 80% inhibition of spike (S1-S2) binding to cells expressing ACE2, assessed by flow cytometry screening assay. The majority of these inhibiting antibodies are derived from the VH3-66 V-gene. The antibody STE90-C11 showed an IC50 of 0.56 nM in a plaque-based live SARS-CoV-2 neutralization assay. The crystal structure of STE90-C11 in complex with SARS-CoV-2-RBD was solved at 2.0 Å resolution showing that the antibody binds at the same region as ACE2 to RBD. In contrast to other published anti-SARS-CoV-2 antibodies, the binding of STE90-C11 is not blocked by known RBD mutations, endowing our antibody with higher intrinsic resistance to those possible escape mutants.

Funding: We kindly acknowledge the financial support of MWK Niedersachsen (14-76103-184CORONA-2/20) for antibody generation. We also acknowledge support of the European Union for the ATAC (“antibody therapy against corona”, Horizon 2020 number 101003650) consortium.

Conflict of Interest: The authors declare a conflict of interest. F.B., D.M.,N.L., S.S., P.A.H., R.B., M.R., K.T.S.,K.D.R.R., S.Z.-E., M.B., V.F., S.T.,M.S. and M.H. are inventors on a patent application on blocking antibodies against SARS-CoV-2. A.H., A.F. and T.S. are officers of CORAT Therapeutics GmbH, a company founded by YUMAB GmbH for the clinical and regulatory development of STE90-C11 (COR-101). A.F., T.S., S.D. and M.H. are shareholders of YUMAB GmbH.

Ethical Approval: Approval number, FV-2020-02. Approved by the TU Braunschweig
Institute for Psychology.

Suggested Citation

Bertoglio, Federico and Fühner, Viola and Ruschig, Maximilian and Heine, Philip Alexander and Rand, Ulfert and Klünemann, Thomas and Meier, Doris and Langreder, Nora and Steinke, Stephan and Ballmann, Rico and Schneider, Kai-Thomas and Roth, Kristian Danial Ralph and Kuhn, Philipp and Riese, Peggy and Schäckermann, Dorina and Korn, Janin and Koch, Allan and Zock-Emmenthal, Susanne and Becker, Marlies and Scholz, Margitta and Moreira, Gustavo Marçal Schmidt Garcia and Wenzel, Esther Veronika and Russo, Giulio and Garritsen, Hendrikus S.P. and Casu, Sebastian and Gerstner, Andreas and Roth, Günter and Hermann, Andreas and Schirrmann, Thomas and Dübel, Stefan and Frenzel, André and Van den Heuvel, Joop and Cicin-Sain, Luka and Schubert, Maren and Hust, Michael, A SARS-CoV-2 Neutralizing Antibody Selected from COVID-19 Patients by Phage Display is Binding to the ACE2-RBD Interface and is Tolerant to Known RBD Mutations. Available at SSRN: https://ssrn.com/abstract=3754550
This is a paper under consideration at Cell Press and has not been peer-reviewed.

Federico Bertoglio

Technology University of Braunschweig - Institut für Biochemie, Biotechnologie und Bioinformatik ( email )

Germany

Viola Fühner

Technology University of Braunschweig - Institut für Biochemie, Biotechnologie und Bioinformatik ( email )

Germany

Maximilian Ruschig

Technology University of Braunschweig - Institut für Biochemie, Biotechnologie und Bioinformatik ( email )

Germany

Philip Alexander Heine

Technology University of Braunschweig - Institut für Biochemie, Biotechnologie und Bioinformatik ( email )

Germany

Ulfert Rand

Helmholtz Centre for Infection Research - Department of Vaccinology and Applied Microbiology

Inhoffenstraße 7
Braunschweig, 38124
Germany

Thomas Klünemann

Helmholtz Centre for Infection Research - Department of Structure and Function of Proteins

Inhoffenstraße 7
Braunschweig, 38124
Germany

Doris Meier

Technology University of Braunschweig - Institut für Biochemie, Biotechnologie und Bioinformatik ( email )

Germany

Nora Langreder

Technology University of Braunschweig - Institut für Biochemie, Biotechnologie und Bioinformatik ( email )

Germany

Stephan Steinke

Technology University of Braunschweig - Institut für Biochemie, Biotechnologie und Bioinformatik ( email )

Germany

Rico Ballmann

Technology University of Braunschweig - Institut für Biochemie, Biotechnologie und Bioinformatik ( email )

Germany

Kai-Thomas Schneider

Technology University of Braunschweig - Institut für Biochemie, Biotechnologie und Bioinformatik ( email )

Germany

Kristian Danial Ralph Roth

Technology University of Braunschweig - Institut für Biochemie, Biotechnologie und Bioinformatik ( email )

Germany

Philipp Kuhn

YUMAB GmbH ( email )

Peggy Riese

Helmholtz Centre for Infection Research - Department of Vaccinology and Applied Microbiology

Inhoffenstraße 7
Braunschweig, 38124
Germany

Dorina Schäckermann

Technology University of Braunschweig - Institut für Biochemie, Biotechnologie und Bioinformatik ( email )

Germany

Janin Korn

Technology University of Braunschweig - Institut für Biochemie, Biotechnologie und Bioinformatik ( email )

Germany

Allan Koch

Technology University of Braunschweig - Institut für Biochemie, Biotechnologie und Bioinformatik ( email )

Germany

Susanne Zock-Emmenthal

Technology University of Braunschweig - Institut für Genetik ( email )

Abt-Jerusalem-Str. 7
Braunschweig, D-38106
Germany

Marlies Becker

Technology University of Braunschweig - Institut für Biochemie, Biotechnologie und Bioinformatik ( email )

Germany

Margitta Scholz

Technology University of Braunschweig - Institut für Biochemie, Biotechnologie und Bioinformatik ( email )

Germany

Gustavo Marçal Schmidt Garcia Moreira

Technology University of Braunschweig - Institut für Biochemie, Biotechnologie und Bioinformatik ( email )

Germany

Esther Veronika Wenzel

Technology University of Braunschweig - Institut für Biochemie, Biotechnologie und Bioinformatik ( email )

Germany

Giulio Russo

Technology University of Braunschweig - Institut für Biochemie, Biotechnologie und Bioinformatik ( email )

Germany

Hendrikus S.P. Garritsen

Städtisches Klinikum Braunschweig gGmbH ( email )

Sebastian Casu

Helios Klinikum Salzgitter ( email )

Andreas Gerstner

Städtisches Klinikum Braunschweig gGmbH ( email )

Günter Roth

BioCopy GmbH

Andreas Hermann

CORAT Therapeutics GmbH

Thomas Schirrmann

YUMAB GmbH ( email )

Stefan Dübel

Technology University of Braunschweig - Institut für Biochemie, Biotechnologie und Bioinformatik ( email )

Germany

André Frenzel

YUMAB GmbH ( email )

Joop Van den Heuvel

Helmholtz Centre for Infection Research - Department of Structure and Function of Proteins

Inhoffenstraße 7
Braunschweig, 38124
Germany

Luka Cicin-Sain

Helmholtz Centre for Infection Research - Department of Vaccinology ( email )

Germany

Maren Schubert

Technology University of Braunschweig - Institut für Biochemie, Biotechnologie und Bioinformatik ( email )

Germany

Michael Hust (Contact Author)

Technology University of Braunschweig - Institut für Biochemie, Biotechnologie und Bioinformatik ( email )

Germany

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