Discovery and characterization of high-affinity, potent SARS-CoV-2 neutralizing antibodies via single B cell screening

Author:

Schardt John S.,Pornnoppadol Ghasidit,Desai Alec A.,Park Kyung Soo,Zupancic Jennifer M.,Makowski Emily K.,Smith Matthew D.,Chen Hongwei,Garcia de Mattos Barbosa Mayara,Cascalho MariliaORCID,Lanigan Thomas M.,Moon James J.,Tessier Peter M.

Abstract

AbstractMonoclonal antibodies that target SARS-CoV-2 with high affinity are valuable for a wide range of biomedical applications involving novel coronavirus disease (COVID-19) diagnosis, treatment, and prophylactic intervention. Strategies for the rapid and reliable isolation of these antibodies, especially potent neutralizing antibodies, are critical toward improved COVID-19 response and informed future response to emergent infectious diseases. In this study, single B cell screening was used to interrogate antibody repertoires of immunized mice and isolate antigen-specific IgG1+ memory B cells. Using these methods, high-affinity, potent neutralizing antibodies were identified that target the receptor-binding domain of SARS-CoV-2. Further engineering of the identified molecules to increase valency resulted in enhanced neutralizing activity. Mechanistic investigation revealed that these antibodies compete with ACE2 for binding to the receptor-binding domain of SARS-CoV-2. These antibodies may warrant further development for urgent COVID-19 applications. Overall, these results highlight the potential of single B cell screening for the rapid and reliable identification of high-affinity, potent neutralizing antibodies for infectious disease applications.

Funder

U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences

NSF Graduate Research Fellowship

MICHR Education PTSP 2020

U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases

COVID-19: CVC Impact Research Ignitor Grant AwardUniversity of Michigan MICHR Accelerating Synergy Award

University of Michigan Institutional Funds

U.S. Department of Health & Human Services | National Institutes of Health

National Science Foundation

Albert M. Mattocks Chair, Biointerfaces Institute

Publisher

Springer Science and Business Media LLC

Subject

Multidisciplinary

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