A Therapeutic Non-self-reactive SARS-CoV-2 Antibody Protects from Lung Pathology in a COVID-19 Hamster Model

被引：248

作者：

Kreye, Jakob ^{[1
,2
,3
,4
,5
,6
,7
]}

Reincke, S. Momsen ^{[1
,2
,3
,4
,5
,6
,8
]}

Kornau, Hans-Christian ^{[1
,4
,5
,6
,9
]}

Sanchez-Sendin, Elisa ^{[1
,2
,3
,4
,5
,6
]}

Corman, Victor Max ^{[4
,5
,6
,10
]}

Liu, Hejun ^{[11
]}

Yuan, Meng ^{[11
]}

Wu, Nicholas C. ^{[11
]}

Zhu, Xueyong ^{[11
]}

Lee, Chang-Chun D. ^{[11
]}

Trimpert, Jakob ^{[12
]}

Hoeltje, Markus ^{[4
,5
,6
,13
]}

Dietert, Kristina ^{[14
,15
]}

Stoeffler, Laura ^{[1
,3
,4
,5
,6
]}

von Wardenburg, Niels ^{[1
,3
,4
,5
,6
]}

van Hoof, Scott ^{[1
,2
,3
,4
,5
,6
]}

Homeyer, Marie A. ^{[1
,3
,4
,5
,6
,8
]}

Hoffmann, Julius ^{[1
,3
,4
,5
,6
]}

Abdelgawad, Azza ^{[12
]}

Gruber, Achim D. ^{[14
]}

Bertzbach, Luca D. ^{[12
]}

Vladimirova, Daria ^{[12
]}

Li, Lucie Y. ^{[2
,4
,5
,6
,13
]}

Barthel, Paula Charlotte ^{[4
,5
,6
,13
]}

Skriner, Karl ^{[4
,5
,6
,16
]}

Hocke, Andreas C. ^{[4
,5
,6
,17
]}

Hippenstiel, Stefan ^{[4
,5
,6
,17
]}

Witzenrath, Martin ^{[4
,5
,6
,17
]}

Suttorp, Norbert ^{[4
,5
,6
,17
]}

Kurth, Florian ^{[4
,5
,6
,17
,18
,19
]}

Franke, Christiana ^{[3
,4
,5
,6
]}

Endres, Matthias ^{[1
,3
,4
,5
,6
,20
,21
,22
,23
,24
,25
]}

Schmitz, Dietmar ^{[1
,4
,5
,6
,9
]}

Jeworowski, Lara Maria ^{[4
,5
,6
,10
]}

Richter, Anja ^{[4
,5
,6
,10
]}

Schmidt, Marie Luisa ^{[4
,5
,6
,10
]}

Schwarz, Tatjana ^{[4
,5
,6
,10
]}

Mueller, Marcel Alexander ^{[4
,5
,6
,10
]}

Drosten, Christian ^{[4
,5
,6
,10
]}

Wendisch, Daniel ^{[4
,5
,6
,17
]}

Sander, Leif E. ^{[4
,5
,6
,17
]}

Osterrieder, Nikolaus ^{[12
,26
]}

Wilson, Ian A. ^{[11
,27
]}

Pruess, Harald ^{[1
,2
,3
,4
,5
,6
]}

机构：

[1] German Ctr Neurodegenerat Dis DZNE Berlin, D-10117 Berlin, Germany

[2] Helmholtz Innovat Lab BaoBab Brain Antibody Omics, D-10117 Berlin, Germany

[3] Charite Univ Med Berlin, Dept Neurol & Expt Neurol, D-10117 Berlin, Germany

[4] Free Univ Berlin, D-10117 Berlin, Germany

[5] Humboldt Univ, D-10117 Berlin, Germany

[6] Berlin Inst Hlth, D-10117 Berlin, Germany

[7] Charite Univ Med Berlin, Dept Pediat Neurol, D-10117 Berlin, Germany

[8] Berlin Inst Hlth BIH, D-10178 Berlin, Germany

[9] Charite Univ Med Berlin, Neurosci Res Ctr NWFZ, Cluster NeuroCure, D-10117 Berlin, Germany

[10] Charite Univ Med Berlin, Inst Virol, D-10117 Berlin, Germany

[11] Scripps Res Inst, Dept Integrat Struct & Computat Biol, La Jolla, CA 92037 USA

[12] Free Univ Berlin, Inst Virol, D-14163 Berlin, Germany

[13] Charite Univ Med Berlin, Inst Integrat Neuroanat Berlin, D-10117 Berlin, Germany

[14] Free Univ Berlin, Inst Vet Pathol, D-14163 Berlin, Germany

[15] Free Univ Berlin, Vet Ctr Resistance Res, D-14163 Berlin, Germany

[16] Charite Univ Med Berlin, Dept Rheumatol & Clin Immunol, D-10117 Berlin, Germany

[17] Charite Univ Med Berlin, Dept Infect Dis & Resp Med, D-10117 Berlin, Germany

[18] Univ Med Ctr Hamburg Eppendorf, Bernhard Nocht Inst Trop Med, Dept Trop Med, D-20359 Hamburg, Germany

[19] Univ Med Ctr Hamburg Eppendorf, Dept Med 1, D-20359 Hamburg, Germany

[20] Charite Univ Med Berlin, Ctr Stroke Res Berlin, D-10117 Berlin, Germany

[21] Charite Univ Med Berlin, Excellence Cluster NeuroCure Berlin, D-10117 Berlin, Germany

[22] Charite Univ Med Berlin, German Ctr Cardiovasc Res DZHK, Partner Site Berlin, D-10785 Berlin, Germany

[23] Free Univ Berlin, D-10785 Berlin, Germany

[24] Humboldt Univ, D-10785 Berlin, Germany

[25] Berlin Inst Hlth, D-10785 Berlin, Germany

[26] City Univ Hong Kong, Jockey Club Coll Vet Med & Life Sci, Dept Infect Dis & Publ Hlth, Hong Kong, Peoples R China

[27] Scripps Res Inst, Skaggs Inst Chem Biol, La Jolla, CA 92037 USA

来源：

CELL | 2020年 / 183卷 / 04期

基金：

美国国家卫生研究院;

关键词：

CORONAVIRUS; BINDING; AUTOANTIBODIES;

D O I：

10.1016/j.cell.2020.09.049

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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 anti-bodies 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 angstrom 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.

引用

页码：1058 / +

页数：31

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