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

被引:132
|
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
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
收藏
页码:915 / 922
页数:8
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