دورية أكاديمية
أعرض في EDS

A Therapeutic Non-self-reactive SARS-CoV-2 Antibody Protects from Lung Pathology in a COVID-19 Hamster Model.

التفاصيل البيبلوغرافية
العنوان: A Therapeutic Non-self-reactive SARS-CoV-2 Antibody Protects from Lung Pathology in a COVID-19 Hamster Model.
المؤلفون: 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.
المصدر: Cell [Cell] 2020 Nov 12; Vol. 183 (4), pp. 1058-1069.e19. Date of Electronic Publication: 2020 Sep 23.
نوع المنشور: 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.
اللغة: English
بيانات الدورية: Publisher: Cell Press Country of Publication: United States NLM ID: 0413066 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1097-4172 (Electronic) Linking ISSN: 00928674 NLM ISO Abbreviation: Cell Subsets: MEDLINE
أسماء مطبوعة: Publication: Cambridge, Ma : Cell Press
Original Publication: Cambridge, MIT Press.
مواضيع طبية MeSH: Antibodies, Monoclonal/*immunology , Antibodies, Viral/*immunology , Betacoronavirus/*metabolism , Coronavirus Infections/*pathology , Pneumonia, Viral/*pathology, Angiotensin-Converting Enzyme 2 ; Animals ; Antibodies, Monoclonal/therapeutic use ; Antibodies, Neutralizing/immunology ; Antibodies, Viral/therapeutic use ; Antigen-Antibody Reactions ; Betacoronavirus/immunology ; Betacoronavirus/pathogenicity ; Binding Sites ; COVID-19 ; Coronavirus Infections/drug therapy ; Coronavirus Infections/virology ; Cricetinae ; Crystallography, X-Ray ; Disease Models, Animal ; Humans ; Kinetics ; Lung/immunology ; Lung/metabolism ; Lung/pathology ; Mice ; Mice, Inbred C57BL ; Molecular Dynamics Simulation ; Pandemics ; Peptidyl-Dipeptidase A/chemistry ; Peptidyl-Dipeptidase A/metabolism ; Pneumonia, Viral/drug therapy ; Pneumonia, Viral/virology ; Protein Binding ; SARS-CoV-2 ; Spike Glycoprotein, Coronavirus/chemistry ; Spike Glycoprotein, Coronavirus/immunology ; Spike Glycoprotein, Coronavirus/metabolism
مستخلص: 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 IC 50 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.
Competing Interests: Declaration of Interests Related to this work, the German Center for Neurodegenerative Diseases (DZNE) and Charité-Universitätsmedizin Berlin have filed a patent application on which J.K., S.M.R., H.-C.K., E.S.-S., V.M.C., M.A.M., D.W., L.E.S., and H.P. are named as inventors.
(Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)
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معلومات مُعتمدة: K99 AI139445 United States AI NIAID NIH HHS; P41 GM103393 United States GM NIGMS NIH HHS
فهرسة مساهمة: Keywords: COVID-19; SARS-CoV-2; autoreactivity; crystal structures; hamster model; monoclonal antibody; neutralizing antibody; post-exposure; self-antigens; self-reactivity
المشرفين على المادة: 0 (Antibodies, Monoclonal)
0 (Antibodies, Neutralizing)
0 (Antibodies, Viral)
0 (Spike Glycoprotein, Coronavirus)
0 (spike protein, SARS-CoV-2)
EC 3.4.15.1 (Peptidyl-Dipeptidase A)
EC 3.4.17.23 (ACE2 protein, human)
EC 3.4.17.23 (Ace2 protein, mouse)
EC 3.4.17.23 (Angiotensin-Converting Enzyme 2)
تواريخ الأحداث: Date Created: 20201015 Date Completed: 20201125 Latest Revision: 20240211
رمز التحديث: 20240211
مُعرف محوري في PubMed: PMC7510528
DOI: 10.1016/j.cell.2020.09.049
PMID: 33058755
قاعدة البيانات: MEDLINE
الوصف
تدمد:1097-4172
DOI:10.1016/j.cell.2020.09.049