Analysis of memory B cells identifies conserved neutralizing epitopes on the N-terminal domain of variant SARS-Cov-2 spike proteins.

Abstract

SARS-CoV-2 infection or vaccination produces neutralizing antibody responses that contribute to better clinical outcomes. The receptor-binding domain (RBD) and the N-terminal domain (NTD) of the spike trimer (S) constitute the two major neutralizing targets for antibodies. Here, we use NTD-specific probes to capture anti-NTD memory B cells in a longitudinal cohort of infected individuals, some of whom were vaccinated. We found 6 complementation groups of neutralizing antibodies. 58% targeted epitopes outside the NTD supersite, 58% neutralized either Gamma or Omicron, and 14% were broad neutralizers that also neutralized Omicron. Structural characterization revealed that broadly active antibodies targeted three epitopes outside the NTD supersite including a class that recognized both the NTD and SD2 domain. Rapid recruitment of memory B cells producing these antibodies into the plasma cell compartment upon re-infection likely contributes to the relatively benign course of subsequent infections with SARS-CoV-2 variants, including Omicron.

• Authors: Zijun Wang, Frauke Muecksch, Alice Cho, Christian Gaebler, Hans-Heinrich Hoffmann, Victor Ramos, Shuai Zong, Melissa Cipolla, Briana Johnson, Fabian Schmidt, Justin DaSilva, Eva Bednarski, Tarek Ben Tanfous, Raphael Raspe, Kaihui Yao, Yu E Lee, Teresia Chen, Martina Turroja, Katrina G Milard, Juan Dizon, Anna Kaczynska, Anna Gazumyan, Thiago Y Oliveira, Charles M Rice, Marina Caskey, Paul D Bieniasz, Theodora Hatziioannou, Christopher O Barnes, Michel C Nussenzweig
• Journal: Immunity (Immunity) Vol. 55 Issue 6 Pg. 998-1012.e8 (06 14 2022) ISSN: 1097-4180 [Electronic] United States
• PMID: 35447092 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.

Chemical References

• Antibodies, Monoclonal
• Antibodies, Neutralizing
• Antibodies, Viral
• Epitopes
• Spike Glycoprotein, Coronavirus
• spike protein, SARS-CoV-2

Topics

• Antibodies, Monoclonal
• Antibodies, Neutralizing
• Antibodies, Viral
• COVID-19
• Epitopes
• Humans
• Memory B Cells
• SARS-CoV-2
• Spike Glycoprotein, Coronavirus