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A Therapeutic Non-self-reactive SARS-CoV-2 Antibody Protects from Lung Pathology in a COVID-19 Hamster Model.
Cell. 2020 11 12; 183(4):1058-1069.e19.Cell

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 10 COVID-19 patients, we identified 40 strongly neutralizing mAbs. The most potent mAb, CV07-209, neutralized authentic SARS-CoV-2 with an IC50 value 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.

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Authors+Show Affiliations

Kreye J
German Center for Neurodegenerative Diseases (DZNE) Berlin, 10117 Berlin, Germany; Helmholtz Innovation Lab BaoBab (Brain Antibody-omics and B-cell Lab), 10117 Berlin, Germany; Department of Neurology and Experimental Neurology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität Berlin, and Berlin Institute of Health, 10117 Berlin, Germany; Department of Pediatric Neurology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität Berlin, and Berlin Institute of Health, 10117 Berlin, Germany. Electronic address: jakob.kreye@dzne.de.
Reincke SM
German Center for Neurodegenerative Diseases (DZNE) Berlin, 10117 Berlin, Germany; Helmholtz Innovation Lab BaoBab (Brain Antibody-omics and B-cell Lab), 10117 Berlin, Germany; Department of Neurology and Experimental Neurology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität Berlin, and Berlin Institute of Health, 10117 Berlin, Germany; Berlin Institute of Health (BIH), 10178 Berlin, Germany.
Kornau HC
German Center for Neurodegenerative Diseases (DZNE) Berlin, 10117 Berlin, Germany; Neuroscience Research Center (NWFZ), Cluster NeuroCure, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität Berlin, and Berlin Institute of Health, 10117 Berlin, Germany.
Sánchez-Sendin E
German Center for Neurodegenerative Diseases (DZNE) Berlin, 10117 Berlin, Germany; Helmholtz Innovation Lab BaoBab (Brain Antibody-omics and B-cell Lab), 10117 Berlin, Germany; Department of Neurology and Experimental Neurology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität Berlin, and Berlin Institute of Health, 10117 Berlin, Germany.
Corman VM
Institute of Virology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, 10117 Berlin, Germany, and German Centre for Infection Research (DZIF), 10117 Berlin, Germany.
Liu H
Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Yuan M
Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Wu NC
Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Zhu X
Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Lee CD
Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Trimpert J
Institute of Virology, Freie Universität Berlin, 14163 Berlin, Germany.
Höltje M
Institute of Integrative Neuroanatomy Berlin, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, 10117 Berlin, Germany.
Dietert K
Institute of Veterinary Pathology, Freie Universität Berlin, 14163 Berlin, Germany; Veterinary Centre for Resistance Research, Freie Universität Berlin, 14163 Berlin, Germany.
Stöffler L
German Center for Neurodegenerative Diseases (DZNE) Berlin, 10117 Berlin, Germany; Department of Neurology and Experimental Neurology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität Berlin, and Berlin Institute of Health, 10117 Berlin, Germany.
von Wardenburg N
German Center for Neurodegenerative Diseases (DZNE) Berlin, 10117 Berlin, Germany; Department of Neurology and Experimental Neurology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität Berlin, and Berlin Institute of Health, 10117 Berlin, Germany.
van Hoof S
German Center for Neurodegenerative Diseases (DZNE) Berlin, 10117 Berlin, Germany; Helmholtz Innovation Lab BaoBab (Brain Antibody-omics and B-cell Lab), 10117 Berlin, Germany; Department of Neurology and Experimental Neurology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität Berlin, and Berlin Institute of Health, 10117 Berlin, Germany.
Homeyer MA
German Center for Neurodegenerative Diseases (DZNE) Berlin, 10117 Berlin, Germany; Department of Neurology and Experimental Neurology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität Berlin, and Berlin Institute of Health, 10117 Berlin, Germany; Berlin Institute of Health (BIH), 10178 Berlin, Germany.
Hoffmann J
German Center for Neurodegenerative Diseases (DZNE) Berlin, 10117 Berlin, Germany; Department of Neurology and Experimental Neurology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität Berlin, and Berlin Institute of Health, 10117 Berlin, Germany.
Abdelgawad A
Institute of Virology, Freie Universität Berlin, 14163 Berlin, Germany.
Gruber AD
Institute of Veterinary Pathology, Freie Universität Berlin, 14163 Berlin, Germany.
Bertzbach LD
Institute of Virology, Freie Universität Berlin, 14163 Berlin, Germany.
Vladimirova D
Institute of Virology, Freie Universität Berlin, 14163 Berlin, Germany.
Li LY
Helmholtz Innovation Lab BaoBab (Brain Antibody-omics and B-cell Lab), 10117 Berlin, Germany; Institute of Integrative Neuroanatomy Berlin, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, 10117 Berlin, Germany.
Barthel PC
Institute of Integrative Neuroanatomy Berlin, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, 10117 Berlin, Germany.
Skriner K
Department of Rheumatology and Clinical Immunology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität Berlin, and Berlin Institute of Health, 10117 Berlin, Germany.
Hocke AC
Department of Infectious Diseases and Respiratory Medicine, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität Berlin, and Berlin Institute of Health, 10117 Berlin, Germany.
Hippenstiel S
Department of Infectious Diseases and Respiratory Medicine, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität Berlin, and Berlin Institute of Health, 10117 Berlin, Germany.
Witzenrath M
Department of Infectious Diseases and Respiratory Medicine, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität Berlin, and Berlin Institute of Health, 10117 Berlin, Germany.
Suttorp N
Department of Infectious Diseases and Respiratory Medicine, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität Berlin, and Berlin Institute of Health, 10117 Berlin, Germany.
Kurth F
Department of Infectious Diseases and Respiratory Medicine, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität Berlin, and Berlin Institute of Health, 10117 Berlin, Germany; Department of Tropical Medicine, Bernhard Nocht Institute for Tropical Medicine and I. Department of Medicine, University Medical Center Hamburg-Eppendorf, 20359 Hamburg, Germany.
Franke C
Department of Neurology and Experimental Neurology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität Berlin, and Berlin Institute of Health, 10117 Berlin, Germany.
Endres M
German Center for Neurodegenerative Diseases (DZNE) Berlin, 10117 Berlin, Germany; Department of Neurology and Experimental Neurology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität Berlin, and Berlin Institute of Health, 10117 Berlin, Germany; Center for Stroke Research Berlin, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität Berlin, and Berlin Institute of Health, 10117 Berlin, Germany; Excellence Cluster NeuroCure Berlin, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität Berlin, and Berlin Institute of Health, 10117 Berlin, Germany; German 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, 10785 Berlin, Germany.
Schmitz D
German Center for Neurodegenerative Diseases (DZNE) Berlin, 10117 Berlin, Germany; Neuroscience Research Center (NWFZ), Cluster NeuroCure, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität Berlin, and Berlin Institute of Health, 10117 Berlin, Germany.
Jeworowski LM
Institute of Virology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, 10117 Berlin, Germany, and German Centre for Infection Research (DZIF), 10117 Berlin, Germany.
Richter A
Institute of Virology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, 10117 Berlin, Germany, and German Centre for Infection Research (DZIF), 10117 Berlin, Germany.
Schmidt ML
Institute of Virology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, 10117 Berlin, Germany, and German Centre for Infection Research (DZIF), 10117 Berlin, Germany.
Schwarz T
Institute of Virology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, 10117 Berlin, Germany, and German Centre for Infection Research (DZIF), 10117 Berlin, Germany.
Müller MA
Institute of Virology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, 10117 Berlin, Germany, and German Centre for Infection Research (DZIF), 10117 Berlin, Germany.
Drosten C
Institute of Virology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, 10117 Berlin, Germany, and German Centre for Infection Research (DZIF), 10117 Berlin, Germany.
Wendisch D
Department of Infectious Diseases and Respiratory Medicine, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität Berlin, and Berlin Institute of Health, 10117 Berlin, Germany.
Sander LE
Department of Infectious Diseases and Respiratory Medicine, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität Berlin, and Berlin Institute of Health, 10117 Berlin, Germany.
Osterrieder N
Institute of Virology, Freie Universität Berlin, 14163 Berlin, Germany; Department of Infectious Diseases and Public Health, Jockey Club College of Veterinary Medicine and Life Sciences, City University of Hong Kong, Hong Kong.
Wilson IA
Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA; The Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Prüss H
German Center for Neurodegenerative Diseases (DZNE) Berlin, 10117 Berlin, Germany; Helmholtz Innovation Lab BaoBab (Brain Antibody-omics and B-cell Lab), 10117 Berlin, Germany; Department of Neurology and Experimental Neurology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität Berlin, and Berlin Institute of Health, 10117 Berlin, Germany. Electronic address: harald.pruess@dzne.de.

MeSH

Angiotensin-Converting Enzyme 2AnimalsAntibodies, MonoclonalAntibodies, NeutralizingAntibodies, ViralAntigen-Antibody ReactionsBetacoronavirusBinding SitesCOVID-19Coronavirus InfectionsCricetinaeCrystallography, X-RayDisease Models, AnimalHumansKineticsLungMiceMice, Inbred C57BLMolecular Dynamics SimulationPandemicsPeptidyl-Dipeptidase APneumonia, ViralProtein BindingSARS-CoV-2Spike Glycoprotein, Coronavirus

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

Language

eng

PubMed ID

33058755

Citation

Kreye, Jakob, et al. "A Therapeutic Non-self-reactive SARS-CoV-2 Antibody Protects From Lung Pathology in a COVID-19 Hamster Model." Cell, vol. 183, no. 4, 2020, pp. 1058-1069.e19.
Kreye J, Reincke SM, Kornau HC, et al. A Therapeutic Non-self-reactive SARS-CoV-2 Antibody Protects from Lung Pathology in a COVID-19 Hamster Model. Cell. 2020;183(4):1058-1069.e19.
Kreye, J., Reincke, S. M., Kornau, H. C., Sánchez-Sendin, E., Corman, V. M., Liu, H., Yuan, M., Wu, N. C., Zhu, X., Lee, C. D., Trimpert, J., Höltje, M., Dietert, K., Stöffler, L., von Wardenburg, N., van Hoof, S., Homeyer, M. A., Hoffmann, J., Abdelgawad, A., ... Prüss, H. (2020). A Therapeutic Non-self-reactive SARS-CoV-2 Antibody Protects from Lung Pathology in a COVID-19 Hamster Model. Cell, 183(4), 1058-e19. https://doi.org/10.1016/j.cell.2020.09.049
Kreye J, et al. A Therapeutic Non-self-reactive SARS-CoV-2 Antibody Protects From Lung Pathology in a COVID-19 Hamster Model. Cell. 2020 11 12;183(4):1058-1069.e19. PubMed PMID: 33058755.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A Therapeutic Non-self-reactive SARS-CoV-2 Antibody Protects from Lung Pathology in a COVID-19 Hamster Model. AU - Kreye,Jakob, AU - Reincke,S Momsen, AU - Kornau,Hans-Christian, AU - Sánchez-Sendin,Elisa, AU - Corman,Victor Max, AU - Liu,Hejun, AU - Yuan,Meng, AU - Wu,Nicholas C, AU - Zhu,Xueyong, AU - Lee,Chang-Chun D, AU - Trimpert,Jakob, AU - Höltje,Markus, AU - Dietert,Kristina, AU - Stöffler,Laura, AU - von Wardenburg,Niels, AU - van Hoof,Scott, AU - Homeyer,Marie A, AU - Hoffmann,Julius, AU - Abdelgawad,Azza, AU - Gruber,Achim D, AU - Bertzbach,Luca D, AU - Vladimirova,Daria, AU - Li,Lucie Y, AU - Barthel,Paula Charlotte, AU - Skriner,Karl, AU - Hocke,Andreas C, AU - Hippenstiel,Stefan, AU - Witzenrath,Martin, AU - Suttorp,Norbert, AU - Kurth,Florian, AU - Franke,Christiana, AU - Endres,Matthias, AU - Schmitz,Dietmar, AU - Jeworowski,Lara Maria, AU - Richter,Anja, AU - Schmidt,Marie Luisa, AU - Schwarz,Tatjana, AU - Müller,Marcel Alexander, AU - Drosten,Christian, AU - Wendisch,Daniel, AU - Sander,Leif E, AU - Osterrieder,Nikolaus, AU - Wilson,Ian A, AU - Prüss,Harald, Y1 - 2020/09/23/ PY - 2020/08/11/received PY - 2020/09/14/revised PY - 2020/09/18/accepted PY - 2020/10/16/pubmed PY - 2020/11/26/medline PY - 2020/10/15/entrez KW - COVID-19 KW - SARS-CoV-2 KW - autoreactivity KW - crystal structures KW - hamster model KW - monoclonal antibody KW - neutralizing antibody KW - post-exposure KW - self-antigens KW - self-reactivity SP - 1058 EP - 1069.e19 JF - Cell JO - Cell VL - 183 IS - 4 N2 - 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 10 COVID-19 patients, we identified 40 strongly neutralizing mAbs. The most potent mAb, CV07-209, neutralized authentic SARS-CoV-2 with an IC50 value 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. SN - 1097-4172 UR - https://www.unboundmedicine.com/medline/citation/33058755/A_Therapeutic_Non_self_reactive_SARS_CoV_2_Antibody_Protects_from_Lung_Pathology_in_a_COVID_19_Hamster_Model_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0092-8674(20)31246-0 DB - PRIME DP - Unbound Medicine ER -