Your browser doesn't support javascript.
loading
A SARS-CoV-2 neutralizing antibody protects from lung pathology in a COVID-19 hamster model.
Kreye, Jakob; Reincke, S Momsen; Kornau, Hans-Christian; Sánchez-Sendin, Elisa; Max Corman, Victor; 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.
Afiliación
  • Kreye J; German Center for Neurodegenerative Diseases (DZNE) Berlin, Berlin, Germany.
  • Reincke SM; Helmholtz Innovation Lab BaoBab (Brain antibody-omics and B-cell Lab), Berlin, Germany.
  • Kornau HC; Department of Neurology and Experimental Neurology, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität Berlin, and Berlin Institute of Health, Berlin, Germany.
  • Sánchez-Sendin E; Department of Pediatric Neurology, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität Berlin, and Berlin Institute of Health, Berlin, Germany.
  • Max Corman V; German Center for Neurodegenerative Diseases (DZNE) Berlin, Berlin, Germany.
  • Liu H; Helmholtz Innovation Lab BaoBab (Brain antibody-omics and B-cell Lab), Berlin, Germany.
  • Yuan M; Department of Neurology and Experimental Neurology, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität Berlin, and Berlin Institute of Health, Berlin, Germany.
  • Wu NC; Berlin Institute of Health (BIH), 10178 Berlin, Germany.
  • Zhu X; German Center for Neurodegenerative Diseases (DZNE) Berlin, Berlin, Germany.
  • Lee CD; Neuroscience Research Center (NWFZ), Cluster NeuroCure, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität Berlin, and Berlin Institute of Health, Berlin, Germany.
  • Trimpert J; German Center for Neurodegenerative Diseases (DZNE) Berlin, Berlin, Germany.
  • Höltje M; Helmholtz Innovation Lab BaoBab (Brain antibody-omics and B-cell Lab), Berlin, Germany.
  • Dietert K; Department of Neurology and Experimental Neurology, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität Berlin, and Berlin Institute of Health, Berlin, Germany.
  • Stöffler L; Institute 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.
  • von Wardenburg N; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
  • van Hoof S; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
  • Homeyer MA; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
  • Hoffmann J; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
  • Abdelgawad A; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
  • Gruber AD; Institute of Virology, Freie Universität Berlin, Robert-von-Ostertag-Str. 7-13, 14163 Berlin, Germany.
  • Bertzbach LD; Institute of Integrative Neuroanatomy Berlin, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.
  • Vladimirova D; Institute of Veterinary Pathology, Freie Universität Berlin, Robert-von-Ostertag-Str. 15, 14163 Berlin, Germany.
  • Li LY; Veterinary Centre for Resistance Research, Freie Universität Berlin, Robert-von-Ostertag-Str. 8, 14163 Berlin, Germany.
  • Barthel PC; German Center for Neurodegenerative Diseases (DZNE) Berlin, Berlin, Germany.
  • Skriner K; Department of Neurology and Experimental Neurology, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität Berlin, and Berlin Institute of Health, Berlin, Germany.
  • Hocke AC; German Center for Neurodegenerative Diseases (DZNE) Berlin, Berlin, Germany.
  • Hippenstiel S; Department of Neurology and Experimental Neurology, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität Berlin, and Berlin Institute of Health, Berlin, Germany.
  • Witzenrath M; German Center for Neurodegenerative Diseases (DZNE) Berlin, Berlin, Germany.
  • Suttorp N; Helmholtz Innovation Lab BaoBab (Brain antibody-omics and B-cell Lab), Berlin, Germany.
  • Kurth F; Department of Neurology and Experimental Neurology, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität Berlin, and Berlin Institute of Health, Berlin, Germany.
  • Franke C; German Center for Neurodegenerative Diseases (DZNE) Berlin, Berlin, Germany.
  • Endres M; Department of Neurology and Experimental Neurology, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität Berlin, and Berlin Institute of Health, Berlin, Germany.
  • Schmitz D; Berlin Institute of Health (BIH), 10178 Berlin, Germany.
  • Jeworowski LM; German Center for Neurodegenerative Diseases (DZNE) Berlin, Berlin, Germany.
  • Richter A; Department of Neurology and Experimental Neurology, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität Berlin, and Berlin Institute of Health, Berlin, Germany.
  • Schmidt ML; Institute of Virology, Freie Universität Berlin, Robert-von-Ostertag-Str. 7-13, 14163 Berlin, Germany.
  • Schwarz T; Institute of Veterinary Pathology, Freie Universität Berlin, Robert-von-Ostertag-Str. 15, 14163 Berlin, Germany.
  • Müller MA; Institute of Virology, Freie Universität Berlin, Robert-von-Ostertag-Str. 7-13, 14163 Berlin, Germany.
  • Drosten C; Institute of Virology, Freie Universität Berlin, Robert-von-Ostertag-Str. 7-13, 14163 Berlin, Germany.
  • Wendisch D; Helmholtz Innovation Lab BaoBab (Brain antibody-omics and B-cell Lab), Berlin, Germany.
  • Sander LE; Institute of Integrative Neuroanatomy Berlin, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.
  • Osterrieder N; Institute of Integrative Neuroanatomy Berlin, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.
  • Wilson IA; Department of Rheumatology and Clinical Immunology, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität Berlin, and Berlin Institute of Health, Berlin, Germany.
  • Prüss H; Department 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.
bioRxiv ; 2020 Aug 16.
Article en En | MEDLINE | ID: mdl-32817952
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 A 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.
Texto completo
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Idioma: En Revista: BioRxiv Año: 2020 Tipo del documento: Article País de afiliación: Alemania
Texto completo
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Idioma: En Revista: BioRxiv Año: 2020 Tipo del documento: Article País de afiliación: Alemania