Isolation of potent SARS-CoV-2 neutralizing antibodies and protection from disease in a small animal model

被引：774

作者：

Rogers, Thomas F. ^{[1
,2
]}

Zhao, Fangzhu ^{[1
,3
,4
]}

Huang, Deli ^{[1
]}

Beutler, Nathan ^{[1
]}

Burns, Alison ^{[1
,3
,4
]}

He, Wan-Ting ^{[1
,3
,4
]}

Limbo, Oliver ^{[3
,5
]}

Smith, Chloe ^{[1
,3
]}

Song, Ge ^{[1
,3
,4
]}

Woehl, Jordan ^{[3
,5
]}

Yang, Linlin ^{[1
]}

Abbott, Robert K. ^{[4
,6
]}

Callaghan, Sean ^{[1
,3
,4
]}

Garcia, Elijah ^{[1
]}

Hurtado, Jonathan ^{[1
,4
,7
]}

Parren, Mara ^{[1
]}

Peng, Linghang ^{[1
]}

Ramirez, Sydney ^{[6
]}

Ricketts, James ^{[1
]}

Ricciardi, Michael J. ^{[8
]}

Rawlings, Stephen A. ^{[2
]}

Wu, Nicholas C. ^{[9
]}

Yuan, Meng ^{[9
]}

Smith, Davey M. ^{[2
]}

Nemazee, David ^{[1
]}

Teijaro, John R. ^{[1
]}

Voss, James E. ^{[1
]}

Wilson, Ian A. ^{[3
,4
,9
]}

Andrabi, Raiees ^{[1
,3
,4
]}

Briney, Bryan ^{[1
,4
,7
]}

Landais, Elise ^{[1
,3
,4
,5
]}

Sok, Devin ^{[1
,3
,4
,5
]}

Jardine, Joseph G. ^{[3
,5
]}

Burton, Dennis R. ^{[1
,3
,4
,10
,11
]}

机构：

[1] Scripps Res Inst, Dept Immunol & Microbiol, La Jolla, CA 92037 USA

[2] Univ Calif San Diego, Dept Med, Div Infect Dis, La Jolla, CA 92037 USA

[3] Scripps Res Inst, IAVI Neutralizing Antibody Ctr, La Jolla, CA 92037 USA

[4] Scripps Res Inst, Consortium HIV AIDS Vaccine Dev CHAVD, La Jolla, CA 92037 USA

[5] IAVI, New York, NY 10004 USA

[6] La Jolla Inst Immunol LJI, Ctr Infect Dis & Vaccine Res, La Jolla, CA 92037 USA

[7] Scripps Res Inst, Ctr Viral Syst Biol, La Jolla, CA 92037 USA

[8] George Washington Univ, Dept Pathol, Washington, DC 20052 USA

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

[10] MIT, Ragon Inst, Massachusetts Gen Hosp, 77 Massachusetts Ave, Cambridge, MA 02139 USA

[11] Harvard Univ, Cambridge, MA 02139 USA

来源：

SCIENCE | 2020年 / 369卷 / 6506期

关键词：

MONOCLONAL-ANTIBODIES; VIRUS-INFECTION; SPIKE; DESIGN;

D O I：

10.1126/science.abc7520

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Countermeasures to prevent and treat coronavirus disease 2019 (COVID-19) are a global health priority. We enrolled a cohort of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-recovered participants, developed neutralization assays to investigate antibody responses, adapted our high-throughput antibody generation pipeline to rapidly screen more than 1800 antibodies, and established an animal model to test protection. We isolated potent neutralizing antibodies (nAbs) to two epitopes on the receptor binding domain (RBD) and to distinct non-RBD epitopes on the spike (S) protein. As indicated by maintained weight and low lung viral titers in treated animals, the passive transfer of a nAb provides protection against disease in high-dose SARS-CoV-2 challenge in Syrian hamsters. The study suggests a role for nAbs in prophylaxis, and potentially therapy, of COVID-19. The nAbs also define protective epitopes to guide vaccine design.

引用

页码：956 / +

页数：47

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