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

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Item Type:Article
Title:A therapeutic non-self-reactive SARS-CoV-2 antibody protects from lung pathology in a COVID-19 hamster model
Creators Name:Kreye, J. and Reincke, S.M. and Kornau, H.C. and Sánchez-Sendin, E. and Corman, V.M. and Liu, H. and Yuan, M. and Wu, N.C. and Zhu, X. and Lee, C.C.D. and Trimpert, J. and Höltje, M. and Dietert, K. and Stöffler, L. and von Wardenburg, N. and van Hoof, S. and Homeyer, M.A. and Hoffmann, J. and Abdelgawad, A. and Gruber, A.D. and Bertzbach, L.D. and Vladimirova, D. and Li, L.Y. and Barthel, P.C. and Skriner, K. and Hocke, A.C. and Hippenstiel, S. and Witzenrath, M. and Suttorp, N. and Kurth, F. and Franke, C. and Endres, M. and Schmitz, D. and Jeworowski, L.M. and Richter, A. and Schmidt, M.L. and Schwarz, T. and Müller, M.A. and Drosten, C. and Wendisch, D. and Sander, L.E. and Osterrieder, N. and Wilson, I.A. and Prüss, H.
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.
Keywords:COVID-19, SARS-CoV-2, Monoclonal Antibody, Neutralizing Antibody, Crystal Structures, Autoreactivity, Self-Reactivity, Self-Antigens, Hamster Model, Post-Exposure, Animals, Hamsters
Source:Cell
ISSN:0092-8674
Publisher:Cell Press
Volume:183
Number:4
Page Range:1058-1069
Date:12 November 2020
Official Publication:https://doi.org/10.1016/j.cell.2020.09.049
PubMed:View item in PubMed

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