SARS-CoV-2 neutralizing human recombinant antibodies selected from pre-pandemic healthy donors binding at RBD-ACE2 interface

Federico Bertoglio, Doris Meier, Nora Langreder, Stephan Steinke, Ulfert Rand, Luca Simonelli, Philip Alexander Heine, Rico Ballmann, Kai-Thomas Schneider, Kristian Daniel Ralph Roth, Maximilian Ruschig, Peggy Riese, Kathrin Eschke, Yeonsu Kim, Dorina Schäckermann, Mattia Pedotti, Philipp Kuhn, Susanne Zock-Emmenthal, Johannes Wöhrle, Normann Kilb, Tobias Herz, Marlies Becker, Martina Grasshoff, Esther Veronika Wenzel, Giulio Russo, Andrea Kröger, Linda Brunotte, Stephan Ludwig, Viola Fühner, Stefan Daniel Krämer, Stefan Dübel, Luca Varani (), Günter Roth (), Luka Čičin-Šain (), Maren Schubert () and Michael Hust ()
Additional contact information
Federico Bertoglio: Abteilung Biotechnologie
Doris Meier: Abteilung Biotechnologie
Nora Langreder: Abteilung Biotechnologie
Stephan Steinke: Abteilung Biotechnologie
Ulfert Rand: Helmholtz Centre for Infection Research
Luca Simonelli: Università della Svizzera italiana (USI)
Philip Alexander Heine: Abteilung Biotechnologie
Rico Ballmann: Abteilung Biotechnologie
Kai-Thomas Schneider: Abteilung Biotechnologie
Kristian Daniel Ralph Roth: Abteilung Biotechnologie
Maximilian Ruschig: Abteilung Biotechnologie
Peggy Riese: Abteilung Biotechnologie
Kathrin Eschke: Helmholtz Centre for Infection Research
Yeonsu Kim: Helmholtz Centre for Infection Research
Dorina Schäckermann: Abteilung Biotechnologie
Mattia Pedotti: Università della Svizzera italiana (USI)
Philipp Kuhn: YUMAB GmbH
Susanne Zock-Emmenthal: Technische Universität Braunschweig, Institut für Genetik
Johannes Wöhrle: BioCopy GmbH
Normann Kilb: BioCopy GmbH
Tobias Herz: BioCopy GmbH
Marlies Becker: Abteilung Biotechnologie
Martina Grasshoff: Helmholtz Centre for Infection Research, Research Group Innate Immunity and Infection
Esther Veronika Wenzel: Abteilung Biotechnologie
Giulio Russo: Abteilung Biotechnologie
Andrea Kröger: Helmholtz Centre for Infection Research, Research Group Innate Immunity and Infection
Linda Brunotte: Westfälische Wilhelms-Universität Münster, Institut für Virologie (IVM)
Stephan Ludwig: Westfälische Wilhelms-Universität Münster, Institut für Virologie (IVM)
Viola Fühner: Abteilung Biotechnologie
Stefan Daniel Krämer: BioCopy GmbH
Stefan Dübel: Abteilung Biotechnologie
Luca Varani: Università della Svizzera italiana (USI)
Günter Roth: BioCopy GmbH
Luka Čičin-Šain: Helmholtz Centre for Infection Research
Maren Schubert: Abteilung Biotechnologie
Michael Hust: Abteilung Biotechnologie

Nature Communications, 2021, vol. 12, issue 1, 1-15

Abstract: Abstract COVID-19 is a severe acute respiratory disease caused by SARS-CoV-2, a new recently emerged sarbecovirus. This virus uses the human ACE2 enzyme as receptor for cell entry, recognizing it with the receptor binding domain (RBD) of the S1 subunit of the viral spike protein. We present the use of phage display to select anti-SARS-CoV-2 spike antibodies from the human naïve antibody gene libraries HAL9/10 and subsequent identification of 309 unique fully human antibodies against S1. 17 antibodies are binding to the RBD, showing inhibition of spike binding to cells expressing ACE2 as scFv-Fc and neutralize active SARS-CoV-2 virus infection of VeroE6 cells. The antibody STE73-2E9 is showing neutralization of active SARS-CoV-2 as IgG and is binding to the ACE2-RBD interface. Thus, universal libraries from healthy human donors offer the advantage that antibodies can be generated quickly and independent from the availability of material from recovering patients in a pandemic situation.

Date: 2021
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DOI: 10.1038/s41467-021-21609-2

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