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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.
  • 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, USA.
  • 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, USA.
  • 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.
Sci Immunol ; 6(66): eabl5842, 2021 Dec 10.
Article in English | MEDLINE | ID: covidwho-1467664
ABSTRACT
Initial exposure to a pathogen elicits an adaptive immune response to control and eradicate the threat. Interrogating the abundance and specificity of the naive B cell repertoire drives understanding of how to mount protective responses. Here, we isolated naive B cells from eight seronegative human donors targeting the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) receptor binding domain (RBD). Single-cell B cell receptor (BCR) sequencing identified diverse gene usage and no restriction on complementarity determining region length. A subset of recombinant antibodies produced by naive B cell precursors bound to SARS-CoV-2 RBD and engaged circulating variants including B.1.1.7, B.1.351, and B.1.617.2, as well as preemergent bat-derived coronaviruses RaTG13, SHC104, and WIV1. By structural characterization of a naive antibody in complex with SARS-CoV-2 spike, we identified a conserved mode of recognition shared with infection-induced antibodies. We found that representative naive antibodies could signal in a B cell activation assay, and by using directed evolution, we could select for a higher-affinity RBD interaction, conferred by a single amino acid change. The minimally mutated, affinity-matured antibodies also potently neutralized SARS-CoV-2. Understanding the SARS-CoV-2 RBD­specific naive repertoire may inform potential responses capable of recognizing future SARS-CoV-2 variants or emerging coronaviruses, enabling the development of pan-coronavirus vaccines aimed at engaging protective germline responses.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: B-Lymphocytes / Coronavirus / SARS-CoV-2 Topics: Vaccines / Variants Limits: Humans Language: English Journal: Sci Immunol Year: 2021 Document Type: Article Affiliation country: Sciimmunol.abl5842

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Full text: Available Collection: International databases Database: MEDLINE Main subject: B-Lymphocytes / Coronavirus / SARS-CoV-2 Topics: Vaccines / Variants Limits: Humans Language: English Journal: Sci Immunol Year: 2021 Document Type: Article Affiliation country: Sciimmunol.abl5842