Memory B cell repertoire for recognition of evolving SARS-CoV-2 spike.

Abstract

Memory B cell reserves can generate protective antibodies against repeated SARS-CoV-2 infections, but with unknown reach from original infection to antigenically drifted variants. We charted memory B cell receptor-encoded antibodies from 19 COVID-19 convalescent subjects against SARS-CoV-2 spike (S) and found seven major antibody competition groups against epitopes recurrently targeted across individuals. Inclusion of published and newly determined structures of antibody-S complexes identified corresponding epitopic regions. Group assignment correlated with cross-CoV-reactivity breadth, neutralization potency, and convergent antibody signatures. Although emerging SARS-CoV-2 variants of concern escaped binding by many members of the groups associated with the most potent neutralizing activity, some antibodies in each of those groups retained affinity-suggesting that otherwise redundant components of a primary immune response are important for durable protection from evolving pathogens. Our results furnish a global atlas of S-specific memory B cell repertoires and illustrate properties driving viral escape and conferring robustness against emerging variants.

• Authors: Pei Tong, Avneesh Gautam, Ian W Windsor, Meghan Travers, Yuezhou Chen, Nicholas Garcia, Noah B Whiteman, Lindsay G A McKay, Nadia Storm, Lauren E Malsick, Anna N Honko, Felipe J N Lelis, Shaghayegh Habibi, Simon Jenni, Yongfei Cai, Linda J Rennick, W Paul Duprex, Kevin R McCarthy, Christy L Lavine, Teng Zuo, Junrui Lin, Adam Zuiani, Jared Feldman, Elizabeth A MacDonald, Blake M Hauser, Anthony Griffths, Michael S Seaman, Aaron G Schmidt, Bing Chen, Donna Neuberg, Goran Bajic, Stephen C Harrison, Duane R Wesemann
• Journal: Cell (Cell) Vol. 184 Issue 19 Pg. 4969-4980.e15 (09 16 2021) ISSN: 1097-4172 [Electronic] United States
• PMID: 34332650 (Publication Type: Journal Article)
• Copyright: Copyright © 2021 Elsevier Inc. All rights reserved.