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
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