Abstract
Delineating the origins and properties of antibodies elicited by SARS-CoV-2 infection and vaccination is critical for understanding their benefits and potential shortcomings. Therefore, we investigate the SARS-CoV-2 spike (S)-reactive B cell repertoire in unexposed individuals by flow cytometry and single-cell sequencing. We show that ∼82% of SARS-CoV-2 S-reactive B cells harbor a naive phenotype, which represents an unusually high fraction of total human naive B cells (∼0.1%). Approximately 10% of these naive S-reactive B cells share an IGHV1-69/IGKV3-11 B cell receptor pairing, an enrichment of 18-fold compared to the complete naive repertoire. Following SARS-CoV-2 infection, we report an average 37-fold enrichment of IGHV1-69/IGKV3-11 B cell receptor pairing in the S-reactive memory B cells compared to the unselected memory repertoire. This class of B cells targets a previously undefined non-neutralizing epitope on the S2 subunit that becomes exposed on S proteins used in approved vaccines when they transition away from the native pre-fusion state because of instability. These findings can help guide the improvement of SARS-CoV-2 vaccines.
【초록키워드】 SARS-CoV-2, Vaccine, vaccination, S protein, antibody, SARS-COV-2 infection, Sequencing, SARS-CoV-2 vaccines, flow cytometry, memory, B cell, phenotype, target, receptor, epitope, Critical, single-cell, S2 subunit, memory B cell, individual, average, help, fraction, pre-fusion, Complete, benefit, approved, elicited, the SARS-CoV-2, 【제목키워드】 antibody, epitope, SARS-CoV-2 spike, conformation, recognize,