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

Author:

Kreye JakobORCID,Reincke S MomsenORCID,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 FlorianORCID,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

Abstract

ABSTRACTThe 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 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.

Publisher

Cold Spring Harbor Laboratory

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