bioRxivImmunology
Memory B cell repertoire for recognition of evolving SARS-CoV-2 spike
P. Tong, A. Gautam, I. Windsor, M. Travers, Y. Chen, N. Garcia, N. Whiteman, L. McKay, F. J. N. Lelis, S. Habibi, Y. Cai, L. J. Rennick, W. P. Duprex, K. McCarthy, C. L. Lavine, T. Zuo, J. Lin, A. Zuiani, J. Feldman, E. A. MacDonald, B. M. Hauser, A. Griffths, M. S. Seaman, A. G. Schmidt, B. Chen, , D. R. Wesemann
Abstract
Memory B cell reserves can generate protective antibodies against repeated SARS-CoV-2 infections, but with an unknown reach from original infection to antigenically drifted variants. We charted memory B cell receptor-encoded monoclonal antibodies (mAbs) from 19 COVID-19 convalescent subjects against SARS-CoV-2 spike (S) and found 7 major mAb competition groups against epitopes recurrently targeted across individuals. Inclusion of published and newly determined structures of mAb-S complexes identified corresponding epitopic regions. Group assignment correlated with cross-CoV-reactivity breadth, neutralization potency, and convergent antibody signatures. mAbs that competed for binding the original S isolate bound differentially to S variants, suggesting the protective importance of otherwise-redundant recognition. The results furnish a global atlas of the S-specific memory B cell repertoire and illustrate properties conferring robustness against emerging SARS-CoV-2 variants.
- organism: human
- assay: proteomics
- research focus: cell type annotation
- research focus: cell-cell communication
- research focus: differential expression
- research focus: gene regulatory network inference
- approach: experimental assay
- approach: statistical model
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