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Naive human B cells engage the receptor binding domain of SARS-CoV-2, variants of concern, and related sarbecoviruses.
Feldman, Jared; Bals, Julia; Altomare, Clara G; St Denis, Kerri; Lam, Evan C; Hauser, Blake M; Ronsard, Larance; Sangesland, Maya; Moreno, Thalia Bracamonte; Okonkwo, Vintus; Hartojo, Nathania; Balazs, Alejandro B; Bajic, Goran; Lingwood, Daniel; Schmidt, Aaron G.
Afiliación
  • Feldman J; Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, 02139, USA.
  • Bals J; Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, 02139, USA.
  • Altomare CG; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029.
  • St Denis K; Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, 02139, USA.
  • Lam EC; Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, 02139, USA.
  • Hauser BM; Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, 02139, USA.
  • Ronsard L; Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, 02139, USA.
  • Sangesland M; Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, 02139, USA.
  • Moreno TB; Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, 02139, USA.
  • Okonkwo V; Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, 02139, USA.
  • Hartojo N; Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, 02139, USA.
  • Balazs AB; Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, 02139, USA.
  • Bajic G; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029.
  • Lingwood D; Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, 02139, USA.
  • Schmidt AG; Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, 02139, USA.
bioRxiv ; 2021 Jul 09.
Article en En | MEDLINE | ID: mdl-33594359
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.
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Idioma: En Revista: BioRxiv Año: 2021 Tipo del documento: Article País de afiliación: Estados Unidos
Texto completo
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Idioma: En Revista: BioRxiv Año: 2021 Tipo del documento: Article País de afiliación: Estados Unidos