@article{e3e5c3b9320a4750a45e9f0e6aaeb296,
title = "A Therapeutic Non-self-reactive SARS-CoV-2 Antibody Protects from Lung Pathology in a COVID-19 Hamster Model",
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 IC50 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 {\AA} 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, autoreactivity, crystal structures, hamster model, monoclonal antibody, neutralizing antibody, post-exposure, self-antigens, self-reactivity",
author = "Jakob Kreye and Reincke, {S. Momsen} and Kornau, {Hans Christian} and Elisa S{\'a}nchez-Sendin and Corman, {Victor Max} and Hejun Liu and Meng Yuan and Wu, {Nicholas C.} and Xueyong Zhu and Lee, {Chang Chun D.} and Jakob Trimpert and Markus H{\"o}ltje and Kristina Dietert and Laura St{\"o}ffler and {von Wardenburg}, Niels and {van Hoof}, Scott and Homeyer, {Marie A.} and Julius Hoffmann and Azza Abdelgawad and Gruber, {Achim D.} and Bertzbach, {Luca D.} and Daria Vladimirova and Li, {Lucie Y.} and Barthel, {Paula Charlotte} and Karl Skriner and Hocke, {Andreas C.} and Stefan Hippenstiel and Martin Witzenrath and Norbert Suttorp and Florian Kurth and Christiana Franke and Matthias Endres and Dietmar Schmitz and Jeworowski, {Lara Maria} and Anja Richter and Schmidt, {Marie Luisa} and Tatjana Schwarz and M{\"u}ller, {Marcel Alexander} and Christian Drosten and Daniel Wendisch and Sander, {Leif E.} and Nikolaus Osterrieder and Wilson, {Ian A.} and Harald Pr{\"u}ss",
note = "Funding Information: We thank Stefanie Bandura, Matthias Sillmann, and Doreen Brandl for excellent technical assistance; Christian Meisel for performing a cardiolipin ELISA; and Martin Barner for assistance with generating the circos plot in Figure S3 B. We acknowledge BIAFFIN GmbH & Co. KG (Kassel, Germany) for performance of SPR measurements and Dr. D{\'e}sir{\'e}e Kunkel from the Flow & Mass Cytometry Core Facility at Charit{\'e}-Universit{\"a}tsmedizin Berlin for support with single-cell sorting. S.M.R. is a participant in the BIH-Charit{\'e} Junior Clinician Scientist Program funded by Charit{\'e} – Universit{\"a}tsmedizin Berlin and the Berlin Institute of Health . Work at Scripps was supported by NIH K99 AI139445 (to N.C.W.) and the Bill and Melinda Gates Foundation OPP1170236 (to I.A.W.). Use of the SSRL, SLAC National Accelerator Laboratory, is supported by the U.S. Department of Energy , Office of Science , Office of Basic Energy Sciences under contract DE-AC02–76SF00515 . The SSRL Structural Molecular Biology Program is supported by the DOE Office of Biological and Environmental Research and the National Institutes of Health , National Institute of General Medical Sciences (including P41GM103393 ). This work was supported by COVID-19 grants from Freie Universit{\"a}t Berlin and Berlin University Alliance (to N.O. and L.E.S.); by the German Research Foundation (DFG) ( SFB-TR84 to A.D.G., A.C.H., S.H., N.S., M.W., C.D., and L.E.S.; EXC2049 to M.E. and D.S.; and PR 1274/2-1 , PR 1274/3-1 , and PR 1274/5-1 to H.P.); by the Helmholtz Association ( ExNet0009 to H.-C.K. and HIL-A03 to H.P.); and by the Federal Ministry of Education and Research ( Connect-Generate 01GM1908D to H.P. and PROVID 01KI20160A and SYMPATH 01ZX1906A to M.W., A.C.H., S.H., N.S., and L.E.S.). Funding Information: We thank Stefanie Bandura, Matthias Sillmann, and Doreen Brandl for excellent technical assistance; Christian Meisel for performing a cardiolipin ELISA; and Martin Barner for assistance with generating the circos plot in Figure S3B. We acknowledge BIAFFIN GmbH & Co. KG (Kassel, Germany) for performance of SPR measurements and Dr. D{\'e}sir{\'e}e Kunkel from the Flow & Mass Cytometry Core Facility at Charit{\'e}-Universit{\"a}tsmedizin Berlin for support with single-cell sorting. S.M.R. is a participant in the BIH-Charit{\'e} Junior Clinician Scientist Program funded by Charit{\'e} – Universit{\"a}tsmedizin Berlin and the Berlin Institute of Health. Work at Scripps was supported by NIH K99 AI139445 (to N.C.W.) and the Bill and Melinda Gates Foundation OPP1170236 (to I.A.W.). Use of the SSRL, SLAC National Accelerator Laboratory, is supported by the U.S. Department of Energy, Office of Science, Office of Basic Energy Sciences under contract DE-AC02–76SF00515. The SSRL Structural Molecular Biology Program is supported by the DOE Office of Biological and Environmental Research and the National Institutes of Health, National Institute of General Medical Sciences (including P41GM103393). This work was supported by COVID-19 grants from Freie Universit{\"a}t Berlin and Berlin University Alliance (to N.O. and L.E.S.); by the German Research Foundation (DFG) (SFB-TR84 to A.D.G. A.C.H. S.H. N.S. M.W. C.D. and L.E.S.; EXC2049 to M.E. and D.S.; and PR 1274/2-1, PR 1274/3-1, and PR 1274/5-1 to H.P.); by the Helmholtz Association (ExNet0009 to H.-C.K. and HIL-A03 to H.P.); and by the Federal Ministry of Education and Research (Connect-Generate 01GM1908D to H.P. and PROVID 01KI20160A and SYMPATH 01ZX1906A to M.W. A.C.H. S.H. N.S. and L.E.S.). Conceptualization, J.K. S.M.R. H.-C.K. V.M.C. J.T. K.D. H.L. M.Y. N.C.W. N.O. I.A.W. and H.P.; Software, J.K. and S.M.R.; Formal Analysis, J.K. S.M.R. H.-C.K. E.S.-S. V.M.C. H.L. M.Y. N.C.W. J.T. M.H. L.D.B. K.D. A.D.G. M.E. D.S. A.D.G. M.A.M. C.D. N.O. I.A.W. and H.P.; Investigation, J.K. S.M.R. H.-C.K. E.S.-S. V.M.C. H.L. M.Y. N.C.W. X.Z. C.-C.D.L. J.T. M.H. K.D. L.S. N.v.W. S.v.H. M.A.H. J.H. A.A. L.D.B. D.V. L.Y.L. P.C.B. A.C.H. K.S. L.M.J. A.R. M.L.S. T.S. and D.W.; Resources, S.H. M.W. N.S. F.K. C.F. M.E. D.S. D.W. L.E.S. and H.P.; Writing – Original Draft, J.K. S.M.R. and H.P.; Writing – Review & Editing, all authors; Supervision, J.K. S.M.R. I.A.W. and H.P. Related to this work, the German Center for Neurodegenerative Diseases (DZNE) and Charit{\'e}-Universit{\"a}tsmedizin Berlin have filed a patent application on which J.K. S.M.R. H.-C.K. E.S.-S. V.M.C. M.A.M. D.W. L.E.S. and H.P. are named as inventors. Publisher Copyright: {\textcopyright} 2020 The Authors",
year = "2020",
month = nov,
day = "12",
doi = "10.1016/j.cell.2020.09.049",
language = "English (US)",
volume = "183",
pages = "1058--1069.e19",
journal = "Cell",
issn = "0092-8674",
publisher = "Cell Press",
number = "4",
}