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A Therapeutic Non-self-reactive SARS-CoV-2 Antibody Protects from Lung Pathology in a COVID-19 Hamster Model.
Kreye, Jakob; Reincke, S Momsen; Kornau, Hans-Christian; Sánchez-Sendin, Elisa; Corman, Victor Max; Liu, Hejun; Yuan, Meng; Wu, Nicholas C; Zhu, Xueyong; Lee, Chang-Chun D; Trimpert, Jakob; Höltje, Markus; Dietert, Kristina; Stöffler, Laura; von Wardenburg, Niels; van Hoof, Scott; Homeyer, Marie A; Hoffmann, Julius; Abdelgawad, Azza; Gruber, Achim D; Bertzbach, Luca D; Vladimirova, Daria; Li, Lucie Y; Barthel, Paula Charlotte; Skriner, Karl; Hocke, Andreas C; Hippenstiel, Stefan; Witzenrath, Martin; Suttorp, Norbert; Kurth, Florian; Franke, Christiana; Endres, Matthias; Schmitz, Dietmar; Jeworowski, Lara Maria; Richter, Anja; Schmidt, Marie Luisa; Schwarz, Tatjana; Müller, Marcel Alexander; Drosten, Christian; Wendisch, Daniel; Sander, Leif E; Osterrieder, Nikolaus; Wilson, Ian A; Prüss, Harald.
  • 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 Universit
  • 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 Universit
  • 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, Germ
  • 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 Universit
  • 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 Universit
  • 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;
  • 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,
  • 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 Med
  • 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;
  • 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, Germ
  • 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 Universit
Cell ; 183(4): 1058-1069.e19, 2020 11 12.
Article in English | MEDLINE | ID: covidwho-785287
Semantic information from SemMedBD (by NLM)
1. Monoclonal Antibodies PART_OF Homo sapiens
Subject
Monoclonal Antibodies
Predicate
PART_OF
Object
Homo sapiens
2. COVID-19 PROCESS_OF Patients
Subject
COVID-19
Predicate
PROCESS_OF
Object
Patients
3. Patients LOCATION_OF Monoclonal Antibodies
Subject
Patients
Predicate
LOCATION_OF
Object
Monoclonal Antibodies
4. Autoantigens PART_OF Mammals
Subject
Autoantigens
Predicate
PART_OF
Object
Mammals
5. Virus-neutralizing Antibody AUGMENTS Severe Acute Respiratory Syndrome
Subject
Virus-neutralizing Antibody
Predicate
AUGMENTS
Object
Severe Acute Respiratory Syndrome
6. Monoclonal Antibodies PART_OF Homo sapiens
Subject
Monoclonal Antibodies
Predicate
PART_OF
Object
Homo sapiens
7. COVID-19 PROCESS_OF Patients
Subject
COVID-19
Predicate
PROCESS_OF
Object
Patients
8. Patients LOCATION_OF Monoclonal Antibodies
Subject
Patients
Predicate
LOCATION_OF
Object
Monoclonal Antibodies
9. Autoantigens PART_OF Mammals
Subject
Autoantigens
Predicate
PART_OF
Object
Mammals
10. Virus-neutralizing Antibody AUGMENTS Severe Acute Respiratory Syndrome
Subject
Virus-neutralizing Antibody
Predicate
AUGMENTS
Object
Severe Acute Respiratory Syndrome
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.
Subject(s)
Keywords

Full text: Available Collection: International databases Database: MEDLINE Main subject: Pneumonia, Viral / Coronavirus Infections / Betacoronavirus / Antibodies, Monoclonal / Antibodies, Viral Language: English Journal: Cell Year: 2020 Document Type: Article

Full text: Available Collection: International databases Database: MEDLINE Main subject: Pneumonia, Viral / Coronavirus Infections / Betacoronavirus / Antibodies, Monoclonal / Antibodies, Viral Language: English Journal: Cell Year: 2020 Document Type: Article