A public antibody class recognizes an S2 epitope exposed on open conformations of SARS-CoV-2 spike

Mathieu Claireaux, Tom G. Caniels, Marlon Gast, Julianna Han, Denise Guerra, Gius Kerster, Barbera D. C. Schaik, Aldo Jongejan, Angela I. Schriek, Marloes Grobben, Philip J. M. Brouwer, Karlijn 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. Taeye, Godelieve J. Bree, Andrew B. Ward, Kwinten Sliepen, Antoine H. C. Kampen, Perry D. Moerland, Rogier W. Sanders () and Marit J. Gils ()
Additional contact information
Mathieu Claireaux: Amsterdam UMC, University of Amsterdam, Department of Medical Microbiology and Infection prevention, Laboratory of Experimental Virology
Tom G. Caniels: Amsterdam UMC, University of Amsterdam, Department of Medical Microbiology and Infection prevention, Laboratory of Experimental Virology
Marlon Gast: Amsterdam UMC, University of Amsterdam, Department of Medical Microbiology and Infection prevention, Laboratory of Experimental Virology
Julianna Han: The Scripps Research Institute
Denise Guerra: Amsterdam UMC, University of Amsterdam, Department of Medical Microbiology and Infection prevention, Laboratory of Experimental Virology
Gius Kerster: Amsterdam UMC, University of Amsterdam, Department of Medical Microbiology and Infection prevention, Laboratory of Experimental Virology
Barbera D. C. Schaik: Amsterdam UMC, University of Amsterdam, Amsterdam Institute for Infection and Immunity, Amsterdam Institute for Public Health
Aldo Jongejan: Amsterdam UMC, University of Amsterdam, Amsterdam Institute for Infection and Immunity, Amsterdam Institute for Public Health
Angela I. Schriek: Amsterdam UMC, University of Amsterdam, Department of Medical Microbiology and Infection prevention, Laboratory of Experimental Virology
Marloes Grobben: Amsterdam UMC, University of Amsterdam, Department of Medical Microbiology and Infection prevention, Laboratory of Experimental Virology
Philip J. M. Brouwer: Amsterdam UMC, University of Amsterdam, Department of Medical Microbiology and Infection prevention, Laboratory of Experimental Virology
Karlijn Straten: Amsterdam UMC, University of Amsterdam, Department of Medical Microbiology and Infection prevention, Laboratory of Experimental Virology
Yoann Aldon: Amsterdam UMC, University of Amsterdam, Department of Medical Microbiology and Infection prevention, Laboratory of Experimental Virology
Joan Capella-Pujol: Amsterdam UMC, University of Amsterdam, Department of Medical Microbiology and Infection prevention, Laboratory of Experimental Virology
Jonne L. Snitselaar: Amsterdam UMC, University of Amsterdam, Department of Medical Microbiology and Infection prevention, Laboratory of Experimental Virology
Wouter Olijhoek: Amsterdam UMC, University of Amsterdam, Department of Medical Microbiology and Infection prevention, Laboratory of Experimental Virology
Aafke Aartse: Amsterdam UMC, University of Amsterdam, Department of Medical Microbiology and Infection prevention, Laboratory of Experimental Virology
Mitch Brinkkemper: Amsterdam UMC, University of Amsterdam, Department of Medical Microbiology and Infection prevention, Laboratory of Experimental Virology
Ilja Bontjer: Amsterdam UMC, University of Amsterdam, Department of Medical Microbiology and Infection prevention, Laboratory of Experimental Virology
Judith A. Burger: Amsterdam UMC, University of Amsterdam, Department of Medical Microbiology and Infection prevention, Laboratory of Experimental Virology
Meliawati Poniman: Amsterdam UMC, University of Amsterdam, Department of Medical Microbiology and Infection prevention, Laboratory of Experimental Virology
Tom P. L. Bijl: Amsterdam UMC, University of Amsterdam, Department of Medical Microbiology and Infection prevention, Laboratory of Experimental Virology
Jonathan L. Torres: The Scripps Research Institute
Jeffrey Copps: The Scripps Research Institute
Isabel Cuella Martin: Amsterdam UMC, University of Amsterdam, Department of Medical Microbiology and Infection prevention, Laboratory of Experimental Virology
Steven W. Taeye: Amsterdam UMC, University of Amsterdam, Department of Medical Microbiology and Infection prevention, Laboratory of Experimental Virology
Godelieve J. Bree: Amsterdam UMC, University of Amsterdam, Amsterdam Institute for Infection and Immunity, Amsterdam Institute for Infection and Immunity
Andrew B. Ward: The Scripps Research Institute
Kwinten Sliepen: Amsterdam UMC, University of Amsterdam, Department of Medical Microbiology and Infection prevention, Laboratory of Experimental Virology
Antoine H. C. Kampen: Amsterdam UMC, University of Amsterdam, Amsterdam Institute for Infection and Immunity, Amsterdam Institute for Public Health
Perry D. Moerland: Amsterdam UMC, University of Amsterdam, Amsterdam Institute for Infection and Immunity, Amsterdam Institute for Public Health
Rogier W. Sanders: Amsterdam UMC, University of Amsterdam, Department of Medical Microbiology and Infection prevention, Laboratory of Experimental Virology
Marit J. Gils: Amsterdam UMC, University of Amsterdam, Department of Medical Microbiology and Infection prevention, Laboratory of Experimental Virology

Nature Communications, 2022, vol. 13, issue 1, 1-15

Abstract: 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.

Date: 2022
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DOI: 10.1038/s41467-022-32232-0

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