National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)
R01 AI146779
米国
引用
ジャーナル: bioRxiv / 年: 2021 タイトル: Naive human B cells engage the receptor binding domain of SARS-CoV-2, variants of concern, and related sarbecoviruses. 著者: 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 ...著者: 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 / 要旨: 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 ...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.