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

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

  • Nat Commun. 2022 Aug 4;13(1):4539. doi: 10.1038/s41467-022-32232-0.
Mathieu Claireaux  # 1 2,  Tom G Caniels  # 1 2,  Marlon de Gast 1 2,  Julianna Han 3,  Denise Guerra 1 2,  Gius Kerster 1 2,  Barbera D C van Schaik 4,  Aldo Jongejan 4,  Angela I Schriek 1 2,  Marloes Grobben 1 2,  Philip J M Brouwer 1 2 3,  Karlijn van der Straten 1 2 5,  Yoann Aldon 1 2,  Joan Capella-Pujol 1 2,  Jonne L Snitselaar 1 2,  Wouter Olijhoek 1 2,  Aafke Aartse 1 2 6,  Mitch Brinkkemper 1 2,  Ilja Bontjer 1 2,  Judith A Burger 1 2,  Meliawati Poniman 1 2,  Tom P L Bijl 1 2,  Jonathan L Torres 3,  Jeffrey Copps 3,  Isabel Cuella Martin 1 2,  Steven W de Taeye 1 2,  Godelieve J de Bree 5,  Andrew B Ward 3,  Kwinten Sliepen 1 2,  Antoine H C van Kampen 4,  Perry D Moerland 4,  Rogier W Sanders 7 8 9,  Marit J van Gils 10 11
Affiliations

Affiliations

  • 1 Amsterdam UMC, University of Amsterdam, Department of Medical Microbiology and Infection prevention, Laboratory of Experimental Virology, Amsterdam, the Netherlands.
  • 2 Amsterdam institute for Infection and Immunity, Infectious diseases, Amsterdam, the Netherlands.
  • 3 Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA, 92037, USA.
  • 4 Bioinformatics Laboratory, Department of Epidemiology and Data Science, Amsterdam UMC, University of Amsterdam, Amsterdam Institute for Infection and Immunity, Amsterdam Institute for Public Health, Amsterdam, the Netherlands.
  • 5 Department of Internal Medicine, Amsterdam UMC, University of Amsterdam, Amsterdam Institute for Infection and Immunity, Amsterdam Institute for Infection and Immunity, Amsterdam, the Netherlands.
  • 6 Department of Virology, Biomedical Primate Research Centre, Rijswijk, The Netherlands.
  • 7 Amsterdam UMC, University of Amsterdam, Department of Medical Microbiology and Infection prevention, Laboratory of Experimental Virology, Amsterdam, the Netherlands. r.w.sanders@amsterdamumc.nl.
  • 8 Amsterdam institute for Infection and Immunity, Infectious diseases, Amsterdam, the Netherlands. r.w.sanders@amsterdamumc.nl.
  • 9 Department of Microbiology and Immunology, Weill Medical College of Cornell University, New York, NY, USA. r.w.sanders@amsterdamumc.nl.
  • 10 Amsterdam UMC, University of Amsterdam, Department of Medical Microbiology and Infection prevention, Laboratory of Experimental Virology, Amsterdam, the Netherlands. m.j.vangils@amsterdamumc.nl.
  • 11 Amsterdam institute for Infection and Immunity, Infectious diseases, Amsterdam, the Netherlands. m.j.vangils@amsterdamumc.nl.
  • # Contributed equally.
PMID: 35927266 DOI: 10.1038/s41467-022-32232-0
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.

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