Naive human B cells can neutralize SARS-CoV-2 through recognition of its receptor binding domain

Feldman, J.; Bals, J.; Denis, K. S.; Lam, E. C.; Hauser, B. M.; Ronsard, L.; Sangesland, M.; Moreno, T. B.; Okonkwo, V.; Hartojo, N.; Balazs, A. B.; Lingwood, D.; Schmidt, A. G.

doi:10.1101/2021.02.02.429458

bioRxiv · 10.1101/2021.02.02.429458

Naive human B cells can neutralize SARS-CoV-2 through recognition of its receptor binding domain

Feldman, J.·Bals, J.·Denis, K. S.·Lam, E. C.·Hauser, B. M.·Ronsard, L.·Sangesland, M.·Moreno, T. B.·Okonkwo, V.·Hartojo, N.·Balazs, A. B.·Lingwood, D.·Schmidt, A. G.

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Abstract

Exposure to a pathogen elicits an adaptive immune response aimed to control and eradicate. Interrogating the abundance and specificity of the naive B cell repertoire contributes to understanding how to potentially elicit protective responses. Here, we isolated naive B cells from 8 seronegative human donors targeting the SARS-CoV-2 receptor-binding domain (RBD). Single B cell analysis showed diverse gene usage with no restricted complementarity determining region lengths. We show that recombinant antibodies engage SARS-CoV-2 RBD, circulating variants, and pre-emergent coronaviruses. Representative antibodies signal in a B cell activation assay and can be affinity matured through directed evolution. Structural analysis of a naive antibody in complex with spike shows a conserved mode of recognition shared with infection-induced antibodies. Lastly, both naive and affinity-matured antibodies can neutralize SARS-CoV-2. Understanding the naive repertoire may inform potential responses recognizing variants or emerging coronaviruses enabling the development of pan-coronavirus vaccines aimed at engaging germline responses. One Sentence SummaryIsolation of antibody germline precursors targeting the receptor binding domain of coronaviruses.

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Feldman, J., Bals, J., Denis, K. S., Lam, E. C., Hauser, B. M., Ronsard, L., Sangesland, M., Moreno, T. B., Okonkwo, V., Hartojo, N., Balazs, A. B., Lingwood, D., Schmidt, A. G.. 2021-02-10. Naive human B cells can neutralize SARS-CoV-2 through recognition of its receptor binding domain. https://doi.org/10.1101/2021.02.02.429458

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