A SARS-CoV-2 neutralizing antibody protects from lung pathology in a COVID-19 hamster model
S Momsen Reincke,
Victor Max Corman,
Nicholas C. Wu,
Chang-Chun D. Lee,
Niels von Wardenburg,
Scott van Hoof,
Marie A Homeyer,
Achim D. Gruber,
Luca D. Bertzbach,
Lucie Y Li,
Paula Charlotte Barthel,
Andreas C Hocke,
Lara Maria Jeworowski,
Marie Luisa Schmidt,
Marcel Alexander Mueller,
Leif E Sander,
Ian A. Wilson,
Posted 16 Aug 2020
bioRxiv DOI: 10.1101/2020.08.15.252320 (published DOI: 10.1016/j.cell.2020.09.049)
Posted 16 Aug 2020
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. ### Competing Interest Statement Related to this work the German Center for Neurodegenerative Diseases (DZNE) and the Charite - Universitaetsmedizin have filed a patent application on which JK, SMR, HCK, ESS, VMC, MAM, DW, LES and HP are named as inventors.
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