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

• Published in: Cell 2021-09, Vol.184 (19), p.4969-4980.e15
• Main Authors: 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.
• Format: Article
• Language: English
• Subjects: antibody; B cell; breadth; COVID-19; cross-reactivity; memory; neutralization; repertoire; SARS-CoV-2; variants
• ISSN: 0092-8674; 1097-4172; 1097-4172
• DOI: 10.1016/j.cell.2021.07.025

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. [Display omitted] •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 Unbiased charting of memory B cell receptor-encoded antibodies from COVID-19 convalescent subjects identifies seven major antibody competition groups recognizing epitopic regions with group assignment correlating with cross-CoV-reactivity breadth and neutralization potency. SARS-CoV-2 variants tend to escape antibodies from groups with the most potent neutralizers, but many retain affinity, showing that redundant components of a primary immune response establish durable protection from evolving pathogens.