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A SARS-CoV-2 neutralizing antibody protects from lung pathology in a COVID-19 hamster model

View ORCID ProfileJakob Kreye, View ORCID ProfileS Momsen Reincke, Hans-Christian Kornau, Elisa Sánchez-Sendin, Victor Max Corman, Hejun Liu, Meng Yuan, Nicholas C. Wu, Xueyong Zhu, Chang-Chun D. Lee, Jakob Trimpert, Markus Höltje, Kristina Dietert, Laura Stöffler, Niels von Wardenburg, Scott van Hoof, Marie A Homeyer, Julius Hoffmann, Azza Abdelgawad, Achim D Gruber, Luca D Bertzbach, Daria Vladimirova, Lucie Y Li, Paula Charlotte Barthel, Karl Skriner, Andreas C Hocke, Stefan Hippenstiel, Martin Witzenrath, Norbert Suttorp, View ORCID ProfileFlorian Kurth, Christiana Franke, Matthias Endres, Dietmar Schmitz, Lara Maria Jeworowski, Anja Richter, Marie Luisa Schmidt, Tatjana Schwarz, Marcel Alexander Müller, Christian Drosten, Daniel Wendisch, Leif E Sander, Nikolaus Osterrieder, Ian A Wilson, Harald Prüss
doi: https://doi.org/10.1101/2020.08.15.252320
Jakob Kreye
1German Center for Neurodegenerative Diseases (DZNE) Berlin, Berlin, Germany
2Helmholtz Innovation Lab BaoBab (Brain antibody-omics and B-cell Lab), Berlin, Germany
3Department of Neurology and Experimental Neurology, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität Berlin, and Berlin Institute of Health, Berlin, Germany
4Department of Pediatric Neurology, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität Berlin, and Berlin Institute of Health, Berlin, Germany
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  • ORCID record for Jakob Kreye
  • For correspondence: jakob.kreye@dzne.de harald.pruess@dzne.de
S Momsen Reincke
1German Center for Neurodegenerative Diseases (DZNE) Berlin, Berlin, Germany
2Helmholtz Innovation Lab BaoBab (Brain antibody-omics and B-cell Lab), Berlin, Germany
3Department of Neurology and Experimental Neurology, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität Berlin, and Berlin Institute of Health, Berlin, Germany
5Berlin Institute of Health (BIH), 10178 Berlin, Germany
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  • ORCID record for S Momsen Reincke
Hans-Christian Kornau
1German Center for Neurodegenerative Diseases (DZNE) Berlin, Berlin, Germany
6Neuroscience Research Center (NWFZ), Cluster NeuroCure, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität Berlin, and Berlin Institute of Health, Berlin, Germany
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Elisa Sánchez-Sendin
1German Center for Neurodegenerative Diseases (DZNE) Berlin, Berlin, Germany
2Helmholtz Innovation Lab BaoBab (Brain antibody-omics and B-cell Lab), Berlin, Germany
3Department of Neurology and Experimental Neurology, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität Berlin, and Berlin Institute of Health, Berlin, Germany
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Victor Max Corman
7Institute of Virology, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany, and German Centre for Infection Research (DZIF), Berlin, Germany
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Hejun Liu
8Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA
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Meng Yuan
8Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA
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Nicholas C. Wu
8Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA
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Xueyong Zhu
8Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA
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Chang-Chun D. Lee
8Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA
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Jakob Trimpert
9Institute of Virology, Freie Universität Berlin, Robert-von-Ostertag-Str. 7-13, 14163 Berlin, Germany
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Markus Höltje
10Institute of Integrative Neuroanatomy Berlin, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany
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Kristina Dietert
11Institute of Veterinary Pathology, Freie Universität Berlin, Robert-von-Ostertag-Str. 15, 14163 Berlin, Germany
12Veterinary Centre for Resistance Research, Freie Universität Berlin, Robert-von-Ostertag-Str. 8, 14163 Berlin, Germany
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Laura Stöffler
1German Center for Neurodegenerative Diseases (DZNE) Berlin, Berlin, Germany
3Department of Neurology and Experimental Neurology, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität Berlin, and Berlin Institute of Health, Berlin, Germany
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Niels von Wardenburg
1German Center for Neurodegenerative Diseases (DZNE) Berlin, Berlin, Germany
3Department of Neurology and Experimental Neurology, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität Berlin, and Berlin Institute of Health, Berlin, Germany
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Scott van Hoof
1German Center for Neurodegenerative Diseases (DZNE) Berlin, Berlin, Germany
2Helmholtz Innovation Lab BaoBab (Brain antibody-omics and B-cell Lab), Berlin, Germany
3Department of Neurology and Experimental Neurology, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität Berlin, and Berlin Institute of Health, Berlin, Germany
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Marie A Homeyer
1German Center for Neurodegenerative Diseases (DZNE) Berlin, Berlin, Germany
3Department of Neurology and Experimental Neurology, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität Berlin, and Berlin Institute of Health, Berlin, Germany
5Berlin Institute of Health (BIH), 10178 Berlin, Germany
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Julius Hoffmann
1German Center for Neurodegenerative Diseases (DZNE) Berlin, Berlin, Germany
3Department of Neurology and Experimental Neurology, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität Berlin, and Berlin Institute of Health, Berlin, Germany
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Azza Abdelgawad
9Institute of Virology, Freie Universität Berlin, Robert-von-Ostertag-Str. 7-13, 14163 Berlin, Germany
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Achim D Gruber
11Institute of Veterinary Pathology, Freie Universität Berlin, Robert-von-Ostertag-Str. 15, 14163 Berlin, Germany
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Luca D Bertzbach
9Institute of Virology, Freie Universität Berlin, Robert-von-Ostertag-Str. 7-13, 14163 Berlin, Germany
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Daria Vladimirova
9Institute of Virology, Freie Universität Berlin, Robert-von-Ostertag-Str. 7-13, 14163 Berlin, Germany
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Lucie Y Li
2Helmholtz Innovation Lab BaoBab (Brain antibody-omics and B-cell Lab), Berlin, Germany
10Institute of Integrative Neuroanatomy Berlin, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany
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Paula Charlotte Barthel
10Institute of Integrative Neuroanatomy Berlin, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany
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Karl Skriner
13Department of Rheumatology and Clinical Immunology, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität Berlin, and Berlin Institute of Health, Berlin, Germany
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Andreas C Hocke
14Department of Infectious Diseases and Respiratory Medicine, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität Berlin, and Berlin Institute of Health, Berlin, Germany
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Stefan Hippenstiel
14Department of Infectious Diseases and Respiratory Medicine, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität Berlin, and Berlin Institute of Health, Berlin, Germany
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Martin Witzenrath
14Department of Infectious Diseases and Respiratory Medicine, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität Berlin, and Berlin Institute of Health, Berlin, Germany
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Norbert Suttorp
14Department of Infectious Diseases and Respiratory Medicine, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität Berlin, and Berlin Institute of Health, Berlin, Germany
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Florian Kurth
14Department of Infectious Diseases and Respiratory Medicine, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität Berlin, and Berlin Institute of Health, Berlin, Germany
15Department of Tropical Medicine, Bernhard Nocht Institute for Tropical Medicine and I. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
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Christiana Franke
3Department of Neurology and Experimental Neurology, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität Berlin, and Berlin Institute of Health, Berlin, Germany
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Matthias Endres
1German Center for Neurodegenerative Diseases (DZNE) Berlin, Berlin, Germany
3Department of Neurology and Experimental Neurology, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität Berlin, and Berlin Institute of Health, Berlin, Germany
16Center for Stroke Research Berlin, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität Berlin, and Berlin Institute of Health, Berlin, Germany
17Excellence Cluster NeuroCure Berlin, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität Berlin, and Berlin Institute of Health, Berlin, Germany
18German Centre for Cardiovascular Research (DZHK), partner site Berlin, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität Berlin, and Berlin Institute of Health, Berlin, Germany
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Dietmar Schmitz
1German Center for Neurodegenerative Diseases (DZNE) Berlin, Berlin, Germany
6Neuroscience Research Center (NWFZ), Cluster NeuroCure, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität Berlin, and Berlin Institute of Health, Berlin, Germany
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Lara Maria Jeworowski
7Institute of Virology, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany, and German Centre for Infection Research (DZIF), Berlin, Germany
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Anja Richter
7Institute of Virology, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany, and German Centre for Infection Research (DZIF), Berlin, Germany
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Marie Luisa Schmidt
7Institute of Virology, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany, and German Centre for Infection Research (DZIF), Berlin, Germany
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Tatjana Schwarz
7Institute of Virology, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany, and German Centre for Infection Research (DZIF), Berlin, Germany
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Marcel Alexander Müller
7Institute of Virology, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany, and German Centre for Infection Research (DZIF), Berlin, Germany
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Christian Drosten
7Institute of Virology, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany, and German Centre for Infection Research (DZIF), Berlin, Germany
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Daniel Wendisch
14Department of Infectious Diseases and Respiratory Medicine, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität Berlin, and Berlin Institute of Health, Berlin, Germany
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Leif E Sander
14Department of Infectious Diseases and Respiratory Medicine, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität Berlin, and Berlin Institute of Health, Berlin, Germany
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Nikolaus Osterrieder
9Institute of Virology, Freie Universität Berlin, Robert-von-Ostertag-Str. 7-13, 14163 Berlin, Germany
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Ian A Wilson
8Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA
19The Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, CA 92037, USA
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Harald Prüss
1German Center for Neurodegenerative Diseases (DZNE) Berlin, Berlin, Germany
2Helmholtz Innovation Lab BaoBab (Brain antibody-omics and B-cell Lab), Berlin, Germany
3Department of Neurology and Experimental Neurology, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität Berlin, and Berlin Institute of Health, Berlin, Germany
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  • For correspondence: jakob.kreye@dzne.de harald.pruess@dzne.de
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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 IC50 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.

Competing Interest Statement

Related to this work the German Center for Neurodegenerative Diseases (DZNE) and the Charite - Universitaetsmedizin have filed a patent application on which JK, SMR, HCK, ESS, VMC, MAM, DW, LES and HP are named as inventors.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC 4.0 International license.
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Posted August 16, 2020.
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A SARS-CoV-2 neutralizing antibody protects from lung pathology in a COVID-19 hamster model
Jakob Kreye, S Momsen Reincke, Hans-Christian Kornau, Elisa Sánchez-Sendin, Victor Max Corman, Hejun Liu, Meng Yuan, Nicholas C. Wu, Xueyong Zhu, Chang-Chun D. Lee, Jakob Trimpert, Markus Höltje, Kristina Dietert, Laura Stöffler, Niels von Wardenburg, Scott van Hoof, Marie A Homeyer, Julius Hoffmann, Azza Abdelgawad, Achim D Gruber, Luca D Bertzbach, Daria Vladimirova, Lucie Y Li, Paula Charlotte Barthel, Karl Skriner, Andreas C Hocke, Stefan Hippenstiel, Martin Witzenrath, Norbert Suttorp, Florian Kurth, Christiana Franke, Matthias Endres, Dietmar Schmitz, Lara Maria Jeworowski, Anja Richter, Marie Luisa Schmidt, Tatjana Schwarz, Marcel Alexander Müller, Christian Drosten, Daniel Wendisch, Leif E Sander, Nikolaus Osterrieder, Ian A Wilson, Harald Prüss
bioRxiv 2020.08.15.252320; doi: https://doi.org/10.1101/2020.08.15.252320
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A SARS-CoV-2 neutralizing antibody protects from lung pathology in a COVID-19 hamster model
Jakob Kreye, S Momsen Reincke, Hans-Christian Kornau, Elisa Sánchez-Sendin, Victor Max Corman, Hejun Liu, Meng Yuan, Nicholas C. Wu, Xueyong Zhu, Chang-Chun D. Lee, Jakob Trimpert, Markus Höltje, Kristina Dietert, Laura Stöffler, Niels von Wardenburg, Scott van Hoof, Marie A Homeyer, Julius Hoffmann, Azza Abdelgawad, Achim D Gruber, Luca D Bertzbach, Daria Vladimirova, Lucie Y Li, Paula Charlotte Barthel, Karl Skriner, Andreas C Hocke, Stefan Hippenstiel, Martin Witzenrath, Norbert Suttorp, Florian Kurth, Christiana Franke, Matthias Endres, Dietmar Schmitz, Lara Maria Jeworowski, Anja Richter, Marie Luisa Schmidt, Tatjana Schwarz, Marcel Alexander Müller, Christian Drosten, Daniel Wendisch, Leif E Sander, Nikolaus Osterrieder, Ian A Wilson, Harald Prüss
bioRxiv 2020.08.15.252320; doi: https://doi.org/10.1101/2020.08.15.252320

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