Journal: Nat Commun / Year: 2022 Title: A public antibody class recognizes an S2 epitope exposed on open conformations of SARS-CoV-2 spike. Authors: Mathieu Claireaux / Tom G Caniels / Marlon de Gast / Julianna Han / Denise Guerra / Gius Kerster / Barbera D C van Schaik / Aldo Jongejan / Angela I Schriek / Marloes Grobben / Philip J M ...Authors: Mathieu Claireaux / Tom G Caniels / Marlon de Gast / Julianna Han / Denise Guerra / Gius Kerster / Barbera D C van Schaik / Aldo Jongejan / Angela I Schriek / Marloes Grobben / Philip J M Brouwer / Karlijn van der Straten / Yoann Aldon / Joan Capella-Pujol / Jonne L Snitselaar / Wouter Olijhoek / Aafke Aartse / Mitch Brinkkemper / Ilja Bontjer / Judith A Burger / Meliawati Poniman / Tom P L Bijl / Jonathan L Torres / Jeffrey Copps / Isabel Cuella Martin / Steven W de Taeye / Godelieve J de Bree / Andrew B Ward / Kwinten Sliepen / Antoine H C van Kampen / Perry D Moerland / Rogier W Sanders / Marit J van Gils / 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 ...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.
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