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Feldman J, Bals J, Altomare CG, et al. Naive human B cells engage the receptor binding domain of SARS-CoV-2, variants of concern, and related sarbecoviruses. bioRxiv. 2021;doi: 10.1101/2021.02.02.429458.
Feldman, J., Bals, J., Altomare, C. G., St Denis, K., Lam, E. C., Hauser, B. M., Ronsard, L., Sangesland, M., Moreno, T. B., Okonkwo, V., Hartojo, N., Balazs, A. B., Bajic, G., Lingwood, D., & Schmidt, A. G. (2021). Naive human B cells engage the receptor binding domain of SARS-CoV-2, variants of concern, and related sarbecoviruses. bioRxiv : the preprint server for biology, . https://doi.org/10.1101/2021.02.02.429458
Feldman, Jared, et al. "Naive human B cells engage the receptor binding domain of SARS-CoV-2, variants of concern, and related sarbecoviruses." bioRxiv : the preprint server for biology vol. (2021). doi: https://doi.org/10.1101/2021.02.02.429458
Feldman J, Bals J, Altomare CG, St Denis K, Lam EC, Hauser BM, Ronsard L, Sangesland M, Moreno TB, Okonkwo V, Hartojo N, Balazs AB, Bajic G, Lingwood D, Schmidt AG. Naive human B cells engage the receptor binding domain of SARS-CoV-2, variants of concern, and related sarbecoviruses. bioRxiv. 2021 Jul 09; doi: 10.1101/2021.02.02.429458. PMID: 33594359; PMCID: PMC7885909.
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bioRxiv. 2021 Jul 09; doi: 10.1101/2021.02.02.429458.

Naive human B cells engage the receptor binding domain of SARS-CoV-2, variants of concern, and related sarbecoviruses.

bioRxiv : the preprint server for biology

Jared Feldman, Julia Bals, Clara G Altomare, Kerri St Denis, Evan C Lam, Blake M Hauser, Larance Ronsard, Maya Sangesland, Thalia Bracamonte Moreno, Vintus Okonkwo, Nathania Hartojo, Alejandro B Balazs, Goran Bajic, Daniel Lingwood, Aaron G Schmidt

Affiliations

  1. Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, 02139, USA.
  2. Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029.
  3. Department of Microbiology, Harvard Medical School, Boston, MA 02115, USA.

PMID: 33594359 PMCID: PMC7885909 DOI: 10.1101/2021.02.02.429458

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.

Conflict of interest statement

Competing interests: Authors declare no competing interests.

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