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

Tong, P.; Gautam, A.; Windsor, I.; Travers, M.; Chen, Y.; Garcia, N.; Whiteman, N.; McKay, L.; Lelis, F. J. N.; Habibi, S.; Cai, Y.; Rennick, L. J.; Duprex, W. P.; McCarthy, K.; Lavine, C. L.; Zuo, T.; Lin, J.; Zuiani, A.; Feldman, J.; MacDonald, E. A.; Hauser, B. M.; Griffths, A.; Seaman, M. S.; Schmidt, A. G.; Chen, B.; Neuberg, D.; Bajic, G.; Harrison, S. C.; Wesemann, D. R.

doi:10.1101/2021.03.10.434840

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bioRxiv · 10.1101/2021.03.10.434840

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

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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.

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Tong, P., Gautam, A., Windsor, I., Travers, M., Chen, Y., Garcia, N., Whiteman, N., McKay, L., Lelis, F. J. N., Habibi, S., Cai, Y., Rennick, L. J., Duprex, W. P., McCarthy, K., Lavine, C. L., Zuo, T., Lin, J., Zuiani, A., Feldman, J., MacDonald, E. A., Hauser, B. M., Griffths, A., Seaman, M. S., Schmidt, A. G., Chen, B., Neuberg, D., Bajic, G., Harrison, S. C., Wesemann, D. R.. 2021-03-10. Memory B cell repertoire for recognition of evolving SARS-CoV-2 spike. https://doi.org/10.1101/2021.03.10.434840

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