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

Wafaa B. Alsoussi(Washington University in St. Louis), Jackson S. Turner(Washington University in St. Louis), James Brett Case(Washington University in St. Louis), Haiyan Zhao(Washington University in St. Louis), Aaron J. Schmitz(Washington University in St. Louis), Julian Q. Zhou(Yale University), Rita E. Chen(Washington University in St. Louis), Tingting Lei(Washington University in St. Louis), Amena A. Rizk(Washington University in St. Louis), Katherine M. McIntire(Washington University in St. Louis), Emma S. Winkler(Washington University in St. Louis), Julie M. Fox(Washington University in St. Louis), Natasha M. Kafai(Washington University in St. Louis), Larissa B. Thackray(Washington University in St. Louis), Ahmed O. Hassan(Washington University in St. Louis), Fatima Amanat(Icahn School of Medicine at Mount Sinai), Florian Krammer(Icahn School of Medicine at Mount Sinai), Corey T. Watson(University of Louisville), Steven H. Kleinstein(Yale University), Daved H. Fremont(Washington University in St. Louis), Michael Diamond(Washington University in St. Louis), Ali H. Ellebedy(Washington University in St. Louis)
The Journal of Immunology
June 26, 2020
Cited by 221Open Access
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Abstract

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.


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