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
  • 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. [email protected].
  • 8. Amsterdam institute for Infection and Immunity, Infectious diseases, Amsterdam, the Netherlands. [email protected].
  • 9. Department of Microbiology and Immunology, Weill Medical College of Cornell University, New York, NY, USA. [email protected].
  • 10. Amsterdam UMC, University of Amsterdam, Department of Medical Microbiology and Infection prevention, Laboratory of Experimental Virology, Amsterdam, the Netherlands. [email protected].
  • 11. Amsterdam institute for Infection and Immunity, Infectious diseases, Amsterdam, the Netherlands. [email protected].
  • # 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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