Rapid isolation and profiling of a diverse panel of human monoclonal antibodies targeting the SARS-CoV-2 spike protein

• Type of Material: Article
• Authors: Seth J Zost, Vanderbilt University; Pavlo Gilchuk, Vanderbilt University; Rita E Chen, Washington University in St. Louis; James B Case, Washington University in St. Louis; Joseph X Reidy, Vanderbilt University; Andrew Trivette, Vanderbilt University; Rachel S Nargi, Vanderbilt University; Rachel E Sutton, Vanderbilt University; Naveenchandra Suryadevara, Vanderbilt University; Elaine C Chen, Vanderbilt University; Elad Binshtein, Vanderbilt University; Swathi Shrihari, Washington University in St. Louis; Mario Ostrowski, University of Toronto; Helen Y Chu, University of Washington; Jonathan E Didier, Berkeley Lights, Inc.; Keith W MacRenaris, Berkeley Lights, Inc.; Taylor Jones, Vanderbilt University; Samuel Day, Vanderbilt University; Luke Myers, Vanderbilt University; F Eun-Hyung Lee, Emory University; Doan Nguyen, Emory University; Ignacio Sanz, Emory University; Doan R Martinez, University of North Carolina; Paul W Rothlauf, Harvard Medical School; Louis-Marie Bloyet, Washington University; Sean PJ Whelan, Harvard Medical School; Ralph S Baric, University of North Carolina; Larissa B Thackray, Washington University in St. Louis; Michael S Diamond, Washington University in St. Louis; Robert H Carnahan, Vanderbilt University; James E Crowe, Vanderbilt University
• Language: English
• Date: 2020-07-10
• Publisher: NATURE PORTFOLIO
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2020, The Author(s), under exclusive licence to Springer Nature America, Inc.
• Final Published Version (URL): http://dx.doi.org/10.1038/s41591-020-0998-x
• Title of Journal or Parent Work: NATURE MEDICINE
• Volume: 26
• Issue: 9
• Start Page: 1422
• End Page: 1427
• Keywords: EPITOPE; POTENT NEUTRALIZATION; MERS-COV; NEUTRALIZING ANTIBODIES; Life Sciences & Biomedicine; Medicine, Research & Experimental; Biochemistry & Molecular Biology; Science & Technology; Cell Biology; SARS CORONAVIRUS; RESPIRATORY SYNDROME CORONAVIRUS; Research & Experimental Medicine; LENGTH INFECTIOUS CDNA; REVERSE GENETICS; STRUCTURAL DEFINITION

Abstract

Antibodies are a principal determinant of immunity for most RNA viruses and have promise to reduce infection or disease during major epidemics. The novel coronavirus SARS-CoV-2 has caused a global pandemic with millions of infections and hundreds of thousands of deaths to date1,2. In response, we used a rapid antibody discovery platform to isolate hundreds of human monoclonal antibodies (mAbs) against the SARS-CoV-2 spike (S) protein. We stratify these mAbs into five major classes on the basis of their reactivity to subdomains of S protein as well as their cross-reactivity to SARS-CoV. Many of these mAbs inhibit infection of authentic SARS-CoV-2 virus, with most neutralizing mAbs recognizing the receptor-binding domain (RBD) of S. This work defines sites of vulnerability on SARS-CoV-2 S and demonstrates the speed and robustness of advanced antibody discovery platforms.