A Potently Neutralizing Antibody Protects Mice against SARS-CoV-2 Infection

被引：136

作者：

Alsoussi, Wafaa B. ^{[1
]}

Turner, Jackson S. ^{[1
]}

Case, James B. ^{[2
]}

Zhao, Haiyan ^{[1
]}

Schmitz, Aaron J. ^{[1
]}

Zhou, Julian Q. ^{[3
]}

Chen, Rita E. ^{[2
]}

Lei, Tingting ^{[1
]}

Rizk, Amena A. ^{[1
]}

McIntire, Katherine M. ^{[1
]}

Winkler, Emma S. ^{[1
,2
]}

Fox, Julie M. ^{[2
]}

Kafai, Natasha M. ^{[1
,2
]}

Thackray, Larissa B. ^{[2
]}

Hassan, Ahmed O. ^{[2
]}

Amanat, Fatima ^{[4
,5
]}

Krammer, Florian ^{[4
]}

Watson, Corey T. ^{[6
]}

Kleinstein, Steven H. ^{[3
,7
,8
]}

Fremont, Daved H. ^{[1
,9
,10
]}

Diamond, Michael S. ^{[1
,2
,9
,11
,12
]}

Ellebedy, Ali H. ^{[1
,9
,11
,12
]}

机构：

[1] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63110 USA

[2] Washington Univ, Sch Med, Dept Med, St Louis, MO 63110 USA

[3] Yale Univ, Yale Sch Med, Interdept Program Computat Biol & Bioinformat, New Haven, CT 06511 USA

[4] Icahn Sch Med Mt Sinai, Dept Microbiol, New York, NY 10024 USA

[5] Icahn Sch Med Mt Sinai, Grad Sch Biomed Sci, New York, NY 10024 USA

[6] Univ Louisville, Sch Med, Dept Biochem & Mol Genet, Louisville, KY 40292 USA

[7] Yale Sch Med, Dept Pathol, New Haven, CT 06511 USA

[8] Yale Sch Med, Dept Immunobiol, New Haven, CT 06511 USA

[9] Washington Univ, Sch Med, Dept Mol Microbiol, St Louis, MO 63110 USA

[10] Washington Univ, Sch Med, Dept Biochem & Mol Biophys, St Louis, MO 63110 USA

[11] Washington Univ, Sch Med, Andrew M & Jane M Bursky Ctr Human Immunol, St Louis, MO 63110 USA

[12] Washington Univ, Sch Med, Immunotherapy Programs, St Louis, MO 63110 USA

来源：

JOURNAL OF IMMUNOLOGY | 2020年 / 205卷 / 04期

基金：

美国国家卫生研究院;

关键词：

MONOCLONAL-ANTIBODIES; SPIKE PROTEIN; CORONAVIRUS; IMMUNOGLOBULIN; EXPRESSION; TOOLKIT; CLONING; COV;

D O I：

10.4049/jimmunol.2000583

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for millions of infections and hundreds of thousands of deaths globally. There are no widely available licensed therapeutics against SARS-CoV-2, highlighting an urgent need for effective interventions. The virus enters host cells through binding of a receptor-binding domain within its trimeric spike glycoprotein to human angiotensin-converting enzyme 2. In this article, we describe the generation and characterization of a panel of murine mAbs directed against the receptor-binding domain. One mAb, 2B04, neutralized wild-type SARS-CoV-2 in vitro with remarkable potency (half-maximal inhibitory concentration of <2 ng/ml). In a murine model of SARS-CoV-2 infection, 2B04 protected challenged animals from weight loss, reduced lung viral load, and blocked systemic dissemination. Thus, 2B04 is a promising candidate for an effective antiviral that can be used to prevent SARS-CoV-2 infection.

引用

页码：915 / 922

页数：8

共 57 条

[1] BASIC LOCAL ALIGNMENT SEARCH TOOL [J].

ALTSCHUL, SF ;

GISH, W ;

MILLER, W ;

MYERS, EW ;

LIPMAN, DJ .

JOURNAL OF MOLECULAR BIOLOGY, 1990, 215 (03) :403-410

[2] The coronavirus spike protein is a class I virus fusion protein: Structural and functional characterization of the fusion core complex [J].

Bosch, BJ ;

van der Zee, R ;

de Haan, CAM ;

Rottier, PJM .

JOURNAL OF VIROLOGY, 2003, 77 (16) :8801-8811

[3] Mouse Genome Database (MGD) 2019 [J].

Bult, Carol J. ;

Blake, Judith A. ;

Smith, Cynthia L. ;

Kadin, James A. ;

Richardson, Joel E. ;

Anagnostopoulos, A. ;

Asabor, R. ;

Baldarelli, R. M. ;

Beal, J. S. ;

Bello, S. M. ;

Blodgett, O. ;

Butler, N. E. ;

Christie, K. R. ;

Corbani, L. E. ;

Creelman, J. ;

Dolan, M. E. ;

Drabkin, H. J. ;

Giannatto, S. L. ;

Hale, P. ;

Hill, D. P. ;

Law, M. ;

Mendoza, A. ;

McAndrews, M. ;

Miers, D. ;

Motenko, H. ;

Ni, L. ;

Onda, H. ;

Perry, M. ;

Recla, J. M. ;

Richards-Smith, B. ;

Sitnikov, D. ;

Tomczuk, M. ;

Tonorio, G. ;

Wilming, L. ;

Zhu, Y. .

NUCLEIC ACIDS RESEARCH, 2019, 47 (D1) :D801-D806

[4] Potent Neutralizing Antibodies against SARS-CoV-2 Identified by High-Throughput Single-Cell Sequencing of Convalescent Patients' B Cells [J].

Cao, Yunlong ;

Su, Bin ;

Guo, Xianghua ;

Sun, Wenjie ;

Deng, Yongqiang ;

Bao, Linlin ;

Zhu, Qinyu ;

Zhang, Xu ;

Zheng, Yinghui ;

Geng, Chenyang ;

Chai, Xiaoran ;

He, Runsheng ;

Li, Xiaofeng ;

Lv, Qi ;

Zhu, Hua ;

Deng, Wei ;

Xu, Yanfeng ;

Wang, Yanjun ;

Qiao, Luxin ;

Tan, Yafang ;

Song, Liyang ;

Wang, Guopeng ;

Du, Xiaoxia ;

Gao, Ning ;

Liu, Jiangning ;

Xiao, Junyu ;

Su, Xiao-dong ;

Du, Zongmin ;

Feng, Yingmei ;

Qin, Chuan ;

Qin, Chengfeng ;

Jin, Ronghua ;

Xie, X. Sunney .

CELL, 2020, 182 (01) :73-+

[5] A familial cluster of pneumonia associated with the 2019 novel coronavirus indicating person-to-person transmission: a study of a family cluster [J].

Chan, Jasper Fuk-Woo ;

Yuan, Shuofeng ;

Kok, Kin-Hang ;

To, Kelvin Kai-Wang ;

Chu, Hin ;

Yang, Jin ;

Xing, Fanfan ;

Liu, Jieling ;

Yip, Cyril Chik-Yan ;

Poon, Rosana Wing-Shan ;

Tsoi, Hoi-Wah ;

Lo, Simon Kam-Fai ;

Chan, Kwok-Hung ;

Poon, Vincent Kwok-Man ;

Chan, Wan-Mui ;

Ip, Jonathan Daniel ;

Cai, Jian-Piao ;

Cheng, Vincent Chi-Chung ;

Chen, Honglin ;

Hui, Christopher Kim-Ming ;

Yuen, Kwok-Yung .

LANCET, 2020, 395 (10223) :514-523

[6] Modernizing Reference Genome Assemblies [J].

Church, Deanna M. ;

Schneider, Valerie A. ;

Graves, Tina ;

Auger, Katherine ;

Cunningham, Fiona ;

Bouk, Nathan ;

Chen, Hsiu-Chuan ;

Agarwala, Richa ;

McLaren, William M. ;

Ritchie, Graham R. S. ;

Albracht, Derek ;

Kremitzki, Milinn ;

Rock, Susan ;

Kotkiewicz, Holland ;

Kremitzki, Colin ;

Wollam, Aye ;

Trani, Lee ;

Fulton, Lucinda ;

Fulton, Robert ;

Matthews, Lucy ;

Whitehead, Siobhan ;

Chow, Will ;

Torrance, James ;

Dunn, Matthew ;

Harden, Glenn ;

Threadgold, Glen ;

Wood, Jonathan ;

Collins, Joanna ;

Heath, Paul ;

Griffiths, Guy ;

Pelan, Sarah ;

Grafham, Darren ;

Eichler, Evan E. ;

Weinstock, George ;

Mardis, Elaine R. ;

Wilson, Richard K. ;

Howe, Kerstin ;

Flicek, Paul ;

Hubbard, Tim .

PLOS BIOLOGY, 2011, 9 (07)

[7] Coronaviruses as the cause of respiratory infections [J].

Corman, V. M. ;

Lienau, J. ;

Witzenrath, M. .

INTERNIST, 2019, 60 (11) :1136-1145

[8] Protective monotherapy against lethal Ebola virus infection by a potently neutralizing antibody [J].

Corti, Davide ;

Misasi, John ;

Mulangu, Sabue ;

Stanley, Daphne A. ;

Kanekiyo, Masaru ;

Wollen, Suzanne ;

Ploquin, Aurelie ;

Doria-Rose, Nicole A. ;

Staupe, Ryan P. ;

Bailey, Michael ;

Shi, Wei ;

Choe, Misook ;

Marcus, Hadar ;

Thompson, Emily A. ;

Cagigi, Alberto ;

Silacci, Chiara ;

Fernandez-Rodriguez, Blanca ;

Perez, Laurent ;

Sallusto, Federica ;

Vanzetta, Fabrizia ;

Agatic, Gloria ;

Cameroni, Elisabetta ;

Kisalu, Neville ;

Gordon, Ingelise ;

Ledgerwood, Julie E. ;

Mascola, John R. ;

Graham, Barney S. ;

Muyembe-Tamfun, Jean-Jacques ;

Trefry, John C. ;

Lanzavecchia, Antonio ;

Sullivan, Nancy J. .

SCIENCE, 2016, 351 (6279) :1339-1342

[9] Longitudinal Analysis of the Human B Cell Response to Ebola Virus Infection [J].

Davis, Carl W. ;

Jackson, Katherine J. L. ;

McElroy, Anita K. ;

Halfmann, Peter ;

Huang, Jessica ;

Chennareddy, Chakravarthy ;

Piper, Ashley E. ;

Leung, Yvonne ;

Albarino, Cesar G. ;

Crozier, Ian ;

Ellebedy, Ali H. ;

Sidney, John ;

Sette, Alessandro ;

Yu, Tianwei ;

Nielsen, Sandra C. A. ;

Goff, Arthur J. ;

Spiropoulou, Christina F. ;

Saphire, Erica Ollman ;

Cavet, Guy ;

Kawaoka, Yoshihiro ;

Mehta, Aneesh K. ;

Glass, Pamela J. ;

Boyd, Scott D. ;

Ahmed, Rafi .

CELL, 2019, 177 (06) :1566-+

[10] Identification of a novel coronavirus in patients with severe acute respiratory syndrome [J].

Drosten, C ;

Günther, S ;

Preiser, W ;

van der Werf, S ;

Brodt, HR ;

Becker, S ;

Rabenau, H ;

Panning, M ;

Kolesnikova, L ;

Fouchier, RAM ;

Berger, A ;

Burguière, AM ;

Cinatl, J ;

Eickmann, M ;

Escriou, N ;

Grywna, K ;

Kramme, S ;

Manuguerra, JC ;

Müller, S ;

Rickerts, V ;

Stürmer, M ;

Vieth, S ;

Klenk, HD ;

Osterhaus, ADME ;

Schmitz, H ;

Doerr, HW .

NEW ENGLAND JOURNAL OF MEDICINE, 2003, 348 (20) :1967-1976

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