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

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

doi:https://doi.org/10.1038/s41467-022-32232-0

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

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. BurgerMeliawati 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

Research output: Contribution to journal › Article › Academic › peer-review

21 Citations (Scopus)

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.

Original language	English
Article number	4539
Journal	Nature communications
Volume	13
Issue number	1
DOIs	https://doi.org/10.1038/s41467-022-32232-0
Publication status	Published - 1 Dec 2022

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@article{8cc3882ef109474ab9a0c69aea17217b,

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

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.",

author = "Mathieu Claireaux and Caniels, {Tom G.} and {de Gast}, Marlon and Julianna Han and Denise Guerra and Gius Kerster and {van Schaik}, {Barbera D. C.} and Aldo Jongejan and Schriek, {Angela I.} and Marloes Grobben and Brouwer, {Philip J. M.} and {van der Straten}, Karlijn and Yoann Aldon and Joan Capella-Pujol and Snitselaar, {Jonne L.} and Wouter Olijhoek and Aafke Aartse and Mitch Brinkkemper and Ilja Bontjer and Burger, {Judith A.} and Meliawati Poniman and Bijl, {Tom P. L.} and Torres, {Jonathan L.} and Jeffrey Copps and Martin, {Isabel Cuella} and {de Taeye}, {Steven W.} and {de Bree}, {Godelieve J.} and Ward, {Andrew B.} and Kwinten Sliepen and {van Kampen}, {Antoine H. C.} and Moerland, {Perry D.} and Sanders, {Rogier W.} and {van Gils}, {Marit J.}",

note = "Funding Information: We thank Single Cell Discoveries (Utrecht, the Netherlands) for help with single-cell RNA sequencing. We thank Drs. Li Wu and Vineet N. Kewal Ramani from the NIH AIDS Reagent Program for kindly providing Ramos B cells and Dr. Andrew McGuire for kindly sharing the pRRL.EuB29 lentiviral vector that was used to transduce Ramos B cells. We thank Prof. S Marieke van Ham and Dr. George Elias (Sanquin, the Netherlands) as well as Dr. Juan J. Garcia Vallejo (Amsterdam UMC, the Netherlands) for their help in developing the combinatorial probe staining strategy. Characterization of the BCR repertoire using RESEDA was carried out on the Dutch national e-infrastructure with the support of SURF Cooperative. We also acknowledge all funders, Netherlands Organization for Scientific Research (NWO) Vici grant (RWS). Bill & Melinda Gates Foundation, Collaboration for AIDS Vaccine Discovery (CAVD) grant INV-002022 (RWS), Amsterdam UMC AMC Fellowship (MJvG), Bill & Melinda Gates Foundation, COVID-19 Wave 2 mAbs grant INV-024617 (MJvG), Fondation Dormeur, Vaduz (MJvG, RWS), Bill & Melinda Gates Foundation, grant INV-004923 (ABW), Netherlands Organization for Scientific Research (NWO) Veni grant (VI.Veni.192.114) (MC). Funding Information: We thank Single Cell Discoveries (Utrecht, the Netherlands) for help with single-cell RNA sequencing. We thank Drs. Li Wu and Vineet N. Kewal Ramani from the NIH AIDS Reagent Program for kindly providing Ramos B cells and Dr. Andrew McGuire for kindly sharing the pRRL.EuB29 lentiviral vector that was used to transduce Ramos B cells. We thank Prof. S Marieke van Ham and Dr. George Elias (Sanquin, the Netherlands) as well as Dr. Juan J. Garcia Vallejo (Amsterdam UMC, the Netherlands) for their help in developing the combinatorial probe staining strategy. Characterization of the BCR repertoire using RESEDA was carried out on the Dutch national e-infrastructure with the support of SURF Cooperative. We also acknowledge all funders, Netherlands Organization for Scientific Research (NWO) Vici grant (RWS). Bill & Melinda Gates Foundation, Collaboration for AIDS Vaccine Discovery (CAVD) grant INV-002022 (RWS), Amsterdam UMC AMC Fellowship (MJvG), Bill & Melinda Gates Foundation, COVID-19 Wave 2 mAbs grant INV-024617 (MJvG), Fondation Dormeur, Vaduz (MJvG, RWS), Bill & Melinda Gates Foundation, grant INV-004923 (ABW), Netherlands Organization for Scientific Research (NWO) Veni grant (VI.Veni.192.114) (MC). Publisher Copyright: {\textcopyright} 2022, The Author(s).",

year = "2022",

month = dec,

day = "1",

doi = "https://doi.org/10.1038/s41467-022-32232-0",

language = "English",

volume = "13",

journal = "Nature communications",

issn = "2041-1723",

publisher = "Nature Publishing Group",

number = "1",

}

Claireaux, M , Caniels, TG , de Gast, M, Han, J, Guerra, D, Kerster, G, van Schaik, BDC , Jongejan, A , Schriek, AI , Grobben, M, Brouwer, PJM, van der Straten, K , Aldon, Y , Capella-Pujol, J , Snitselaar, JL , Olijhoek, W , Aartse, A , Brinkkemper, M , Bontjer, I , Burger, JA , Poniman, M, Bijl, TPL, Torres, JL, Copps, J, Martin, IC, de Taeye, SW , de Bree, GJ, Ward, AB, Sliepen, K , van Kampen, AHC , Moerland, PD , Sanders, RW & van Gils, MJ 2022, 'A public antibody class recognizes an S2 epitope exposed on open conformations of SARS-CoV-2 spike', Nature communications, vol. 13, no. 1, 4539. https://doi.org/10.1038/s41467-022-32232-0

TY - JOUR

T1 - A public antibody class recognizes an S2 epitope exposed on open conformations of SARS-CoV-2 spike

AU - Claireaux, Mathieu

AU - Caniels, Tom G.

AU - de Gast, Marlon

AU - Han, Julianna

AU - Guerra, Denise

AU - Kerster, Gius

AU - van Schaik, Barbera D. C.

AU - Jongejan, Aldo

AU - Schriek, Angela I.

AU - Grobben, Marloes

AU - Brouwer, Philip J. M.

AU - van der Straten, Karlijn

AU - Aldon, Yoann

AU - Capella-Pujol, Joan

AU - Snitselaar, Jonne L.

AU - Olijhoek, Wouter

AU - Aartse, Aafke

AU - Brinkkemper, Mitch

AU - Bontjer, Ilja

AU - Burger, Judith A.

AU - Poniman, Meliawati

AU - Bijl, Tom P. L.

AU - Torres, Jonathan L.

AU - Copps, Jeffrey

AU - Martin, Isabel Cuella

AU - de Taeye, Steven W.

AU - de Bree, Godelieve J.

AU - Ward, Andrew B.

AU - Sliepen, Kwinten

AU - van Kampen, Antoine H. C.

AU - Moerland, Perry D.

AU - Sanders, Rogier W.

AU - van Gils, Marit J.

N1 - Funding Information: We thank Single Cell Discoveries (Utrecht, the Netherlands) for help with single-cell RNA sequencing. We thank Drs. Li Wu and Vineet N. Kewal Ramani from the NIH AIDS Reagent Program for kindly providing Ramos B cells and Dr. Andrew McGuire for kindly sharing the pRRL.EuB29 lentiviral vector that was used to transduce Ramos B cells. We thank Prof. S Marieke van Ham and Dr. George Elias (Sanquin, the Netherlands) as well as Dr. Juan J. Garcia Vallejo (Amsterdam UMC, the Netherlands) for their help in developing the combinatorial probe staining strategy. Characterization of the BCR repertoire using RESEDA was carried out on the Dutch national e-infrastructure with the support of SURF Cooperative. We also acknowledge all funders, Netherlands Organization for Scientific Research (NWO) Vici grant (RWS). Bill & Melinda Gates Foundation, Collaboration for AIDS Vaccine Discovery (CAVD) grant INV-002022 (RWS), Amsterdam UMC AMC Fellowship (MJvG), Bill & Melinda Gates Foundation, COVID-19 Wave 2 mAbs grant INV-024617 (MJvG), Fondation Dormeur, Vaduz (MJvG, RWS), Bill & Melinda Gates Foundation, grant INV-004923 (ABW), Netherlands Organization for Scientific Research (NWO) Veni grant (VI.Veni.192.114) (MC). Funding Information: We thank Single Cell Discoveries (Utrecht, the Netherlands) for help with single-cell RNA sequencing. We thank Drs. Li Wu and Vineet N. Kewal Ramani from the NIH AIDS Reagent Program for kindly providing Ramos B cells and Dr. Andrew McGuire for kindly sharing the pRRL.EuB29 lentiviral vector that was used to transduce Ramos B cells. We thank Prof. S Marieke van Ham and Dr. George Elias (Sanquin, the Netherlands) as well as Dr. Juan J. Garcia Vallejo (Amsterdam UMC, the Netherlands) for their help in developing the combinatorial probe staining strategy. Characterization of the BCR repertoire using RESEDA was carried out on the Dutch national e-infrastructure with the support of SURF Cooperative. We also acknowledge all funders, Netherlands Organization for Scientific Research (NWO) Vici grant (RWS). Bill & Melinda Gates Foundation, Collaboration for AIDS Vaccine Discovery (CAVD) grant INV-002022 (RWS), Amsterdam UMC AMC Fellowship (MJvG), Bill & Melinda Gates Foundation, COVID-19 Wave 2 mAbs grant INV-024617 (MJvG), Fondation Dormeur, Vaduz (MJvG, RWS), Bill & Melinda Gates Foundation, grant INV-004923 (ABW), Netherlands Organization for Scientific Research (NWO) Veni grant (VI.Veni.192.114) (MC). Publisher Copyright: © 2022, The Author(s).

PY - 2022/12/1

Y1 - 2022/12/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85135399910&partnerID=8YFLogxK

U2 - https://doi.org/10.1038/s41467-022-32232-0

DO - https://doi.org/10.1038/s41467-022-32232-0

M3 - Article

C2 - 35927266

SN - 2041-1723

VL - 13

JO - Nature communications

JF - Nature communications

IS - 1

M1 - 4539

ER -

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

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