학술논문
Memory B cell repertoire for recognition of evolving SARS-CoV-2 spike
Document Type
Report
Author
Tong, Pei; Gautam, Avneesh; Windsor, Ian W.; Travers, Meghan; Chen, Yuezhou; Garcia, Nicholas; Whiteman, Noah B.; McKay, Lindsay G.A.; Storm, Nadia; Malsick, Lauren E.; Honko, Anna N.; Lelis, Felipe J.N.; Habibi, Shaghayegh; Jenni, Simon; Cai, Yongfei; Rennick, Linda J.; Duprex, W. Paul; McCarthy, Kevin R.; Lavine, Christy L.; Zuo, Teng; Lin, Junrui; Zuiani, Adam; Feldman, Jared; MacDonald, Elizabeth A.; Hauser, Blake M.; Griffths, Anthony; Seaman, Michael S.; Schmidt, Aaron G.; Chen, Bing; Neuberg, Donna; Bajic, Goran; Harrison, Stephen C.; Wesemann, Duane R.
Source
Cell. September 16, 2021, Vol. 184 Issue 19, 4969
Subject
Language
English
ISSN
0092-8674
Abstract
Keywords antibody; memory; B cell; COVID-19; SARS-CoV-2; repertoire; breadth; variants; cross-reactivity; neutralization Highlights * Seven major epitopic regions of SARS-CoV-2 spike are consistently targeted by human Abs * Ab group assignment correlates with CoV binding breadth and neutralization potency * SARS-CoV-2 variants tend to escape Abs from the groups with most potent neutralizers * Intra-group Ab binding redundancy confers robustness against emerging variants Summary 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.