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

Autor: 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
Přispěvatelé: Medical Microbiology and Infection Prevention, AII - Infectious diseases, Graduate School, Epidemiology and Data Science, AII - Inflammatory diseases, APH - Methodology, APH - Personalized Medicine, Experimental Immunology, Infectious diseases, APH - Aging & Later Life, APH - Global Health
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: Nature communications, 13(1):4539. Nature Publishing Group
ISSN: 2041-1723
Popis: 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.
Databáze: OpenAIRE