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Naive human B cells can neutralize SARS-CoV-2 through recognition of its receptor binding domain
Jared Feldman; Julia Bals; Clara 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.
Afiliação
  • Jared Feldman; Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, 02139, USA
  • Julia Bals; Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, 02139, USA
  • Clara Altomare; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029
  • Kerri St. Denis; Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, 02139, USA
  • Evan C. Lam; Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, 02139, USA
  • Blake M. Hauser; Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, 02139, USA
  • Larance Ronsard; Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, 02139, USA
  • Maya Sangesland; Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, 02139, USA
  • Thalia Bracamonte Moreno; Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, 02139, USA
  • Vintus Okonkwo; Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, 02139, USA
  • Nathania Hartojo; Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, 02139, USA
  • Alejandro B. Balazs; Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, 02139, USA
  • Goran Bajic; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029
  • Daniel Lingwood; Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, 02139, USA
  • Aaron G. Schmidt; Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, 02139, USA; Department of Microbiology, Harvard Medical School, Boston, MA 02115, USA
Preprint em En | PREPRINT-BIORXIV | ID: ppbiorxiv-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. One Sentence SummaryIsolation of antibody germline precursors targeting the receptor binding domain of coronaviruses.
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Texto completo: 1 Coleções: 09-preprints Base de dados: PREPRINT-BIORXIV Idioma: En Ano de publicação: 2021 Tipo de documento: Preprint
Texto completo
Adicionar na Minha BVS
Imprimir
XML
Buscar no Google
Texto completo: 1 Coleções: 09-preprints Base de dados: PREPRINT-BIORXIV Idioma: En Ano de publicação: 2021 Tipo de documento: Preprint