Analysis of a SARS-CoV-2-Infected Individual Reveals Development of Potent Neutralizing Antibodies with Limited Somatic Mutation

Emilie Seydoux, Leah J. Homad, Anna J. MacCamy, K. Rachael Parks, Nicholas K. Hurlburt, Madeleine F. Jennewein, Nicholas R. Akins, Andrew B. Stuart, Yu Hsin Wan, Junli Feng, Rachael E. Whaley, Suruchi Singh, Michael Boeckh, Kristen W. Cohen, M. Juliana McElrath, Janet A. Englund, Helen Y. Chu, Marie Pancera, Andrew T. McGuire, Leonidas Stamatatos

Research output: Contribution to journalArticle

Abstract

Copyright © 2020 Elsevier Inc. All rights reserved. Antibody responses develop following SARS-CoV-2 infection, but little is known about their epitope specificities, clonality, binding affinities, epitopes, and neutralizing activity. We isolated B cells specific for the SARS-CoV-2 envelope glycoprotein spike (S) from a COVID-19-infected subject 21 days after the onset of clinical disease. 45 S-specific monoclonal antibodies were generated. They had undergone minimal somatic mutation with limited clonal expansion, and three bound the receptor-binding domain (RBD). Two antibodies neutralized SARS-CoV-2. The most potent antibody bound the RBD and prevented binding to the ACE2 receptor, while the other bound outside the RBD. Thus, most anti-S antibodies that were generated in this patient during the first weeks of COVID-19 infection were non-neutralizing and target epitopes outside the RBD. Antibodies that disrupt the SARS-CoV-2 S-ACE2 interaction can potently neutralize the virus without undergoing extensive maturation. Such antibodies have potential preventive and/or therapeutic potential and can serve as templates for vaccine design.
Original languageEnglish
JournalImmunity
DOIs
StatePublished - 8 Jun 2020

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    Seydoux, E., Homad, L. J., MacCamy, A. J., Parks, K. R., Hurlburt, N. K., Jennewein, M. F., Akins, N. R., Stuart, A. B., Wan, Y. H., Feng, J., Whaley, R. E., Singh, S., Boeckh, M., Cohen, K. W., McElrath, M. J., Englund, J. A., Chu, H. Y., Pancera, M., McGuire, A. T., & Stamatatos, L. (2020). Analysis of a SARS-CoV-2-Infected Individual Reveals Development of Potent Neutralizing Antibodies with Limited Somatic Mutation. Immunity. https://doi.org/10.1016/j.immuni.2020.06.001