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10.1126/sciimmunol.abl5842

http://scihub22266oqcxt.onion/10.1126/sciimmunol.abl5842
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suck abstract from ncbi


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pmid34648356      Sci+Immunol 2021 ; 6 (66): eabl5842
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  • Naive human B cells engage the receptor binding domain of SARS-CoV-2, variants of concern, and related sarbecoviruses #MMPMID34648356
  • 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
  • Sci Immunol 2021[Dec]; 6 (66): eabl5842 PMID34648356show ga
  • 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 RBD-specific 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.
  • |Antibodies, Neutralizing/immunology[MESH]
  • |Antigens, Viral/immunology[MESH]
  • |B-Lymphocytes/*cytology/*immunology/metabolism[MESH]
  • |COVID-19 Vaccines/immunology[MESH]
  • |COVID-19/immunology[MESH]
  • |Coronavirus/*immunology[MESH]
  • |Epitopes[MESH]
  • |Humans[MESH]
  • |Lymphocyte Activation[MESH]
  • |SARS-CoV-2/classification/*immunology/metabolism[MESH]


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