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A therapeutic non-self-reactive SARS-CoV-2 antibody protects from lung pathology in a COVID-19 hamster model

Authors

  • J. Kreye
  • S.M. Reincke
  • H.C. Kornau
  • E. Sánchez-Sendin
  • V.M. Corman
  • H. Liu
  • M. Yuan
  • N.C. Wu
  • X. Zhu
  • C.C.D. Lee
  • J. Trimpert
  • M. Höltje
  • K. Dietert
  • L. Stöffler
  • N. von Wardenburg
  • S. van Hoof
  • M.A. Homeyer
  • J. Hoffmann
  • A. Abdelgawad
  • A.D. Gruber
  • L.D. Bertzbach
  • D. Vladimirova
  • L.Y. Li
  • P.C. Barthel
  • K. Skriner
  • A.C. Hocke
  • S. Hippenstiel
  • M. Witzenrath
  • N. Suttorp
  • F. Kurth
  • C. Franke
  • M. Endres
  • D. Schmitz
  • L.M. Jeworowski
  • A. Richter
  • M.L. Schmidt
  • T. Schwarz
  • M.A. Müller
  • C. Drosten
  • D. Wendisch
  • L.E. Sander
  • N. Osterrieder
  • I.A. Wilson
  • H. Prüss

Journal

  • Cell

Citation

  • Cell 183 (4): 1058-1069

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 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.


DOI

doi:10.1016/j.cell.2020.09.049