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

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

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:	Kreye, J. ORCID: https://orcid.org/0000-0003-2913-1015, Reincke, S.M. ORCID: https://orcid.org/0000-0002-8132-3527, Kornau, H.C. ORCID: https://orcid.org/0000-0003-4187-7549, Sánchez-Sendin, E., Corman, V.M. ORCID: https://orcid.org/0000-0002-3605-0136, Liu, H., Yuan, M. ORCID: https://orcid.org/0000-0001-9754-4503, Wu, N.C., Zhu, X., Lee, C.C.D., Trimpert, J. ORCID: https://orcid.org/0000-0003-1616-0810, Höltje, M., Dietert, K., Stöffler, L., von Wardenburg, N., van Hoof, S., Homeyer, M.A., Hoffmann, J., Abdelgawad, A., Gruber, A.D., Bertzbach, L.D. ORCID: https://orcid.org/0000-0002-0698-5395, Vladimirova, D., Li, L.Y., Barthel, P.C. ORCID: https://orcid.org/0000-0001-9463-2284, Skriner, K., Hocke, A.C., Hippenstiel, S. ORCID: https://orcid.org/0000-0002-5146-1064, Witzenrath, M., Suttorp, N., Kurth, F., Franke, C. ORCID: https://orcid.org/0000-0002-5609-2472, Endres, M., Schmitz, D. ORCID: https://orcid.org/0000-0003-2741-5241, Jeworowski, L.M., Richter, A., Schmidt, M.L., Schwarz, T., Müller, M.A., Drosten, C., Wendisch, D., Sander, L.E., Osterrieder, N. ORCID: https://orcid.org/0000-0002-5313-2176, 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, Cricetinae, Mice
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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