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.