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

被引：131

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

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