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A Sars-Cov-2 Neutralizing Antibody Protects from Lung Pathology in a Covid-19 Hamster Model

70 Pages Posted: 26 Aug 2020 Publication Status: Published

See all articles by Jakob Kreye

Jakob Kreye

German Center for Neurodegenerative Diseases (DZNE)

S. Momsen Reincke

German Center for Neurodegenerative Diseases (DZNE) Berlin\

Hans-Christian Kornau

German Center for Neurodegenerative Diseases (DZNE) Berlin

Elisa Sánchez-Sendin

German Center for Neurodegenerative Diseases (DZNE) Berlin

Victor M. Corman

Charité - Universitätsmedizin Berlin - Institute of Virology

Hejun Liu

The Scripps Research Institute - Department of Integrative Structural and Computational Biology

Meng Yuan

Department of Integrative Structural and Computational Biology, The Scripps Research Institute

Nicholas C. Wu

Department of Integrative Structural and Computational Biology, The Scripps Research Institute

Xueyong Zhu

Wuhan University - Department of Cardiology

Chang-Chun D. Lee

Department of Integrative Structural and Computational Biology, The Scripps Research Institute

Jakob Trimpert

Free University of Berlin (FUB) - Institut für Virologie

Markus Höltje

Institute of Integrative Neuroanatomy Berlin, Charité-Universitätsmedizin Berlin

Kristina Dietert

Free University of Berlin (FUB) - Institut für Tierpathologie

Laura Stöffler

German Center for Neurodegenerative Diseases (DZNE) Berlin

Niels von Wardenburg

German Center for Neurodegenerative Diseases (DZNE) Berlin

Scott van Hoof

German Center for Neurodegenerative Diseases (DZNE) Berlin; German Center for Neurodegenerative Diseases (DZNE) Berlin

Marie A. Homeyer

German Center for Neurodegenerative Diseases (DZNE) Berlin

Julius Hoffmann

German Center for Neurodegenerative Diseases (DZNE) Berlin

Azza Abdelgawad

Free University of Berlin (FUB) - Institut für Virologie

Achim Gruber

Free University of Berlin (FUB) - Institut für Tierpathologie

Luca Bertzbach

Free University of Berlin (FUB) - Institut für Virologie

Daria Vladimirova

Free University of Berlin (FUB) - Institut für Virologie

Lucie Y. Li

Helmholtz Innovation Lab BaoBab (Brain antibody-omics and B-cell Lab)

Paula Charlotte Barthel

Institute of Integrative Neuroanatomy Berlin, Charité-Universitätsmedizin Berlin

Karl Skriner

Department of Rheumatology and Clinical Immunology, Charité-Universitätsmedizin Berlin

Andreas C. Hocke

Charité - Universitätsmedizin Berlin - Department of Infectious Diseases and Respiratory Medicine

Stefan Hippenstiel

Charité - Universitätsmedizin Berlin - Department of Infectious Diseases and Respiratory Medicine

Martin Witzenrath

Charité - Universitätsmedizin Berlin - Department of Infectious Diseases and Respiratory Medicine

Norbert Suttorp

Charité - Universitätsmedizin Berlin - Department of Infectious Diseases and Respiratory Medicine

Florian Kurth

Department of Infectious Diseases and Respiratory Medicine, Charité –Universitätsmedizin Berlin

Christiana Franke

Department of Neurology and Experimental Neurology, Charité-Universitätsmedizin Berlin

Matthias Endres

Charité - Universitätsmedizin Berlin - Klinik und Hochschulambulanz für Neurologie

Dietmar Schmitz

Neuroscience Research Center NWFZ; Charité - Universitätsmedizin Berlin - NeuroCure Cluster of Excellence

Lara Maria Jeworowski

Institute of Virology, Charité-Universitätsmedizin Berlin

Anja Richter

Institute of Virology, Charité-Universitätsmedizin Berlin

Marie Luisa Schmidt

Charité - Universitätsmedizin Berlin - Institute of Virology

Tatjana Schwarz

Institute of Virology, Charité-Universitätsmedizin Berlin

Marcel Alexander Müller

Department of Infectious Diseases and Respiratory Medicine, Charité-Universitätsmedizin Berlin

Christian Drosten

Charité - Universitätsmedizin Berlin - Institute of Virology

Daniel Wendisch

Department of Infectious Diseases and Respiratory Medicine, Charité-Universitätsmedizin Berlin

Leif E. Sander

Charité - Universitätsmedizin Berlin - Department of Infectious Diseases and Respiratory Medicine

Nikolaus Osterrieder

Free University of Berlin (FUB) - Institut für Virologie

Ian A Wilson

Department of Integrative Structural and Computational Biology, The Scripps Research Institute

Harald Prüss

German Center for Neurodegenerative Diseases (DZNE)

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Abstract

The emergence of SARS-CoV-2 led to pandemic spread of coronavirus disease 2019 (COVID-19), manifesting with respiratory symptoms and multi-organ dysfunction. Detailed characterization of virus-neutralizing antibodies and target epitopes is needed to understand COVID-19 pathophysiology and guide immunization strategies. Among 598 human monoclonal antibodies (mAbs) from ten COVID-19 patients, we identified 40 strongly neutralizing mAbs. The most potent mAb CV07-209 neutralized authentic SARS-CoV-2 with IC 50 of 3.1 ng/ml. Crystal structures of two mAbs in complex with the SARS-CoV-2 receptor-binding domain at 2.55 and 2.70 Å revealed a direct block of ACE2 attachment. Interestingly, some of the near-germline SARS-CoV-2 neutralizing mAbs reacted with mammalian self-antigens. Prophylactic and therapeutic application of CV07-209 protected hamsters from SARS-CoV-2 infection, weight loss and lung pathology. Our results show that non-self-reactive virus-neutralizing mAbs elicited during SARS-CoV-2 infection are a promising therapeutic strategy.

Keywords: COVID-19, SARS-COV-2, monoclonal antibody, neutralizing antibody, B cell, hamster

Suggested Citation

Kreye, Jakob and Reincke, S. Momsen and Kornau, Hans-Christian and Sánchez-Sendin, Elisa and Corman, Victor M. and Liu, Hejun and Yuan, Meng and Wu, Nicholas C. and Zhu, Xueyong and Lee, Chang-Chun D. and Trimpert, Jakob and Höltje, Markus and Dietert, Kristina and Stöffler, Laura and von Wardenburg, Niels and van Hoof, Scott and Homeyer, Marie A. and Hoffmann, Julius and Abdelgawad, Azza and Gruber, Achim and Bertzbach, Luca and Vladimirova, Daria and Li, Lucie Y. and Barthel, Paula Charlotte and Skriner, Karl and Hocke, Andreas C. and Hippenstiel, Stefan and Witzenrath, Martin and Suttorp, Norbert and Kurth, Florian and Franke, Christiana and Endres, Matthias and Schmitz, Dietmar and Jeworowski, Lara Maria and Richter, Anja and Schmidt, Marie Luisa and Schwarz, Tatjana and Müller, Marcel Alexander and Drosten, Christian and Wendisch, Daniel and Sander, Leif E. and Osterrieder, Nikolaus and Wilson, Ian A and Prüss, Harald, A Sars-Cov-2 Neutralizing Antibody Protects from Lung Pathology in a Covid-19 Hamster Model. Available at SSRN: https://ssrn.com/abstract=3680870 or http://dx.doi.org/10.2139/ssrn.3680870
This version of the paper has not been formally peer reviewed.

Jakob Kreye (Contact Author)

German Center for Neurodegenerative Diseases (DZNE) ( email )

Venusberg-Campus 1, Building 99
Bonn, 53127
Germany

S. Momsen Reincke

German Center for Neurodegenerative Diseases (DZNE) Berlin\ ( email )

Hans-Christian Kornau

German Center for Neurodegenerative Diseases (DZNE) Berlin ( email )

Elisa Sánchez-Sendin

German Center for Neurodegenerative Diseases (DZNE) Berlin ( email )

Victor M. Corman

Charité - Universitätsmedizin Berlin - Institute of Virology ( email )

Hejun Liu

The Scripps Research Institute - Department of Integrative Structural and Computational Biology ( email )

Meng Yuan

Department of Integrative Structural and Computational Biology, The Scripps Research Institute

Nicholas C. Wu

Department of Integrative Structural and Computational Biology, The Scripps Research Institute ( email )

Xueyong Zhu

Wuhan University - Department of Cardiology

238 Jiefang Road, Wuchang District
Wuhan, Hubei 430060
China

Chang-Chun D. Lee

Department of Integrative Structural and Computational Biology, The Scripps Research Institute ( email )

Jakob Trimpert

Free University of Berlin (FUB) - Institut für Virologie ( email )

Germany

Markus Höltje

Institute of Integrative Neuroanatomy Berlin, Charité-Universitätsmedizin Berlin ( email )

Kristina Dietert

Free University of Berlin (FUB) - Institut für Tierpathologie ( email )

Van't-Hoff-Str. 8
Berlin, Berlin 14195
Germany

Laura Stöffler

German Center for Neurodegenerative Diseases (DZNE) Berlin ( email )

Niels Von Wardenburg

German Center for Neurodegenerative Diseases (DZNE) Berlin ( email )

Scott Van Hoof

German Center for Neurodegenerative Diseases (DZNE) Berlin ( email )

German Center for Neurodegenerative Diseases (DZNE) Berlin ( email )

Marie A. Homeyer

German Center for Neurodegenerative Diseases (DZNE) Berlin ( email )

Julius Hoffmann

German Center for Neurodegenerative Diseases (DZNE) Berlin ( email )

Azza Abdelgawad

Free University of Berlin (FUB) - Institut für Virologie ( email )

Germany

Achim Gruber

Free University of Berlin (FUB) - Institut für Tierpathologie ( email )

Van't-Hoff-Str. 8
Berlin, Berlin 14195
Germany

Luca Bertzbach

Free University of Berlin (FUB) - Institut für Virologie ( email )

Germany

Daria Vladimirova

Free University of Berlin (FUB) - Institut für Virologie ( email )

Germany

Lucie Y. Li

Helmholtz Innovation Lab BaoBab (Brain antibody-omics and B-cell Lab) ( email )

Paula Charlotte Barthel

Institute of Integrative Neuroanatomy Berlin, Charité-Universitätsmedizin Berlin ( email )

Karl Skriner

Department of Rheumatology and Clinical Immunology, Charité-Universitätsmedizin Berlin ( email )

Andreas C. Hocke

Charité - Universitätsmedizin Berlin - Department of Infectious Diseases and Respiratory Medicine ( email )

Stefan Hippenstiel

Charité - Universitätsmedizin Berlin - Department of Infectious Diseases and Respiratory Medicine ( email )

Berlin
Germany

Martin Witzenrath

Charité - Universitätsmedizin Berlin - Department of Infectious Diseases and Respiratory Medicine ( email )

Norbert Suttorp

Charité - Universitätsmedizin Berlin - Department of Infectious Diseases and Respiratory Medicine

Florian Kurth

Department of Infectious Diseases and Respiratory Medicine, Charité –Universitätsmedizin Berlin

Christiana Franke

Department of Neurology and Experimental Neurology, Charité-Universitätsmedizin Berlin ( email )

Matthias Endres

Charité - Universitätsmedizin Berlin - Klinik und Hochschulambulanz für Neurologie ( email )

Dietmar Schmitz

Neuroscience Research Center NWFZ

Charitéplatz 1
Berlin, 10117
Germany

Charité - Universitätsmedizin Berlin - NeuroCure Cluster of Excellence

Charitéplatz 1
Hufelandweg 14
Berlin, 10117
Germany

Lara Maria Jeworowski

Institute of Virology, Charité-Universitätsmedizin Berlin ( email )

Anja Richter

Institute of Virology, Charité-Universitätsmedizin Berlin

Marie Luisa Schmidt

Charité - Universitätsmedizin Berlin - Institute of Virology ( email )

Tatjana Schwarz

Institute of Virology, Charité-Universitätsmedizin Berlin ( email )

Marcel Alexander Müller

Department of Infectious Diseases and Respiratory Medicine, Charité-Universitätsmedizin Berlin ( email )

Christian Drosten

Charité - Universitätsmedizin Berlin - Institute of Virology ( email )

Berlin
Germany

Daniel Wendisch

Department of Infectious Diseases and Respiratory Medicine, Charité-Universitätsmedizin Berlin ( email )

Leif E. Sander

Charité - Universitätsmedizin Berlin - Department of Infectious Diseases and Respiratory Medicine ( email )

Nikolaus Osterrieder

Free University of Berlin (FUB) - Institut für Virologie ( email )

Germany

Ian A Wilson

Department of Integrative Structural and Computational Biology, The Scripps Research Institute

Harald Prüss

German Center for Neurodegenerative Diseases (DZNE) ( email )

Venusberg-Campus 1, Building 99
Bonn, 53127
Germany

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