Multi-clonal SARS-CoV-2 neutralization by antibodies isolated from severe COVID-19 convalescent donors

Michael Mor, Michal Werbner, Joel Alter, Modi Safra, Elad Chomsky, Jamie C. Lee, Smadar Hada-Neeman, Ksenia Polonsky, Cameron J. Nowell, Alex E. Clark, Anna Roitburd-Berman, Noam Ben-Shalom, Michal Navon, Dor Rafael, Hila Sharim, Evgeny Kiner, Eric R. Griffis, Jonathan M. Gershoni, Oren Kobiler, Sandra Lawrynowicz LeibelOren Zimhony, Aaron F. Carlin, Gur Yaari, Moshe Dessau, Meital Gal-Tanamy, David Hagin, Ben A. Croker, Natalia T. Freund

Research output: Contribution to journalArticlepeer-review

26 Scopus citations

Abstract

The interactions between antibodies, SARS-CoV-2 and immune cells contribute to the pathogenesis of COVID-19 and protective immunity. To understand the differences between antibody responses in mild versus severe cases of COVID-19, we analyzed the B cell responses in patients 1.5 months post SARS-CoV-2 infection. Severe, and not mild, infection correlated with high titers of IgG against Spike receptor binding domain (RBD) that were capable of ACE2:RBD inhibition. B cell receptor (BCR) sequencing revealed that VH3-53 was enriched during severe infection. Of the 22 antibodies cloned from two severe donors, six exhibited potent neutralization against authentic SARS-CoV-2, and inhibited syncytia formation. Using peptide libraries, competition ELISA and mutagenesis of RBD, we mapped the epitopes of the neutralizing antibodies (nAbs) to three different sites on the Spike. Finally, we used combinations of nAbs targeting different immune-sites to efficiently block SARS-CoV-2 infection. Analysis of 49 healthy BCR repertoires revealed that the nAbs germline VHJH precursors comprise up to 2.7% of all VHJHs. We demonstrate that severe COVID-19 is associated with unique BCR signatures and multi-clonal neutralizing responses that are relatively frequent in the population. Moreover, our data support the use of combination antibody therapy to prevent and treat COVID-19.

Original languageEnglish
Article numbere1009165
JournalPLoS Pathogens
Volume17
Issue number2
DOIs
StatePublished - Feb 2021

Bibliographical note

Publisher Copyright:
Copyright: © 2021 Mor et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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