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    A SARS-CoV-2 neutralizing antibody protects from lung pathology in a COVID-19 hamster model (2020)

    Art
    Zeitschriftenartikel / wissenschaftlicher Beitrag
    Autoren
    Kreye, Jakob
    Reincke, Momsen
    Kornau, Hans-Christian
    Sánchez-Sendin, Elisa
    Max Corman, Victor
    Liu, Hejun
    Yuan, Meng
    Wu, Nicholas C.
    Zhu, Xueyong
    Lee, Chang-Chun David
    Trimpert, Jakob (WE 5)
    Höltje, Markus
    Dietert, Kristina (Tiermedizinisches Zentrum für Resistenzforschung)
    Stöffler, Laura
    von Wardenburg, Niels
    van Hoof, Scott
    Homeyer, Marie A.
    Hoffmann, Julius
    Abdelgawad, Azza
    Gruber, Achim (WE 12)
    Bertzbach, Luca Danilo
    Vladimirova, Daria (WE 5)
    Li, Lucie Y.
    Barthel, Paula Charlotte
    Skriner, Karl
    Hocke, Andreas
    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 Erik
    Osterrieder, Klaus (WE 5)
    Wilson, Ian
    Prüss, Harald
    Quelle
    Cell
    Bandzählung: 183
    Heftzählung: 4
    Seiten: 1058 – 1069
    ISSN: 0092-8674
    Sprache
    Englisch
    Verweise
    URL (Volltext): https://pubmed.ncbi.nlm.nih.gov/32817952/
    DOI: 10.1101/2020.08.15.252320
    Pubmed: 32817952
    Kontakt
    Institut für Tierpathologie

    Robert-von-Ostertag-Str. 15
    14163 Berlin
    +49 30 838 62450
    pathologie@vetmed.fu-berlin.de

    Abstract / Zusammenfassung

    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.