ArticleNature communications2022
A public antibody class recognizes an S2 epitope exposed on open conformations of SARS-CoV-2 spike.
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Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.
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54citing papers in PubMed
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54 citing papers in PubMed, 72 citations in OpenAlex.
- Structural basis of diverse antibody recognition of conserved coronavirus spike S2 epitopes that contribute to protective immunity.bioRxiv : the preprint server for biology · 2026Article
- Structural and functional characterization of a conserved cryptic epitope on SARS-CoV-2 spike S2 subunit.PLoS pathogens · 2026Article
- HKU1 immune imprinting is associated with post-COVID symptoms after SARS-CoV-2 infection.iScience · 2026Article
- SARS-CoV-2 crossreactive B-cells outnumber seasonal coronavirus spike-specific clones at the end of the COVID-19 pandemic.Npj viruses · 2026Article
- Humoral and cellular immune response after COVID-19 vaccination in patients with sickle cell disease on hydroxyurea.Blood advances · 2026Article
- The buried S2 apex of SARS-CoV-2 spike elicits an immunodominant germline-restricted public antibody response.bioRxiv : the preprint server for biology · 2026Article
- Class switching toward IgG4 six months after primary mRNA-based COVID-19 vaccination in kidney patients.PloS one · 2026Article
- SARS-CoV-2-specific B cell responses in non-draining lymph nodes and antibody functionalities in immunized end-stage renal disease patients.Scientific reports · 2025Article
- Common cold embecovirus imprinting primes broadly neutralizing antibody responses to SARS-CoV-2 S2.The Journal of experimental medicine · 2025Article
- Development of ACE2-tropic-betacoronavirus therapeutics for future pandemic preparedness.Nature communications · 2025Article
- Editor's Choice Platform for identifying human glycan-specific antibodies against bacterial pathogens using synthetic glycan fragments.Glycobiology · 2025Article
- Extracorporeal Photopheresis in Solid Organ Transplantation: Modulating B-cell Responses to Improve Graft Survival.Transplantation direct · 2025Article
- TNF inhibitors affect the induction and maintenance of spike-specific B-cell responses after mRNA vaccination.RMD open · 2025Article
- Review
- Deep profiling of B cells responding to various pathogens uncovers compartments in IgG memory B cell and antibody-secreting lineages.Science advances · 2025Article
- Structural Immunology of SARS-CoV-2.Immunological reviews · 2025Review
- Plant-produced SARS-CoV-2 antibody engineered towards enhanced potency and in vivo efficacy.Plant biotechnology journal · 2025Article
- Broadening sarbecovirus neutralization with bispecific antibodies combining distinct conserved targets on the receptor binding domain.Human vaccines & immunotherapeutics · 2024Article
- Deep immunoglobulin repertoire sequencing depicts a comprehensive atlas of spike-specific antibody lineages shared among COVID-19 convalescents.Emerging microbes & infections · 2024Article
- Discovery and characterization of a pan-betacoronavirus S2-binding antibody.Structure (London, England : 1993) · 2024Article
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Authors and funding
33 authors at 5 institutions in 3 countries.
Mathieu Claireaux *Amsterdam UMC, University of Amsterdam, Department of Medical Microbiology and Infection prevention, Laboratory of Experimental Virology, Amsterdam, the Netherlands.ORCID http://orcid.org/0000-0003-1890-9493
Tom G Caniels *Amsterdam UMC, University of Amsterdam, Department of Medical Microbiology and Infection prevention, Laboratory of Experimental Virology, Amsterdam, the Netherlands.ORCID http://orcid.org/0000-0001-9580-157X
Marlon de GastAmsterdam UMC, University of Amsterdam, Department of Medical Microbiology and Infection prevention, Laboratory of Experimental Virology, Amsterdam, the Netherlands.
Julianna HanDepartment of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA, 92037, USA.ORCID http://orcid.org/0000-0002-3402-2609
Denise GuerraAmsterdam UMC, University of Amsterdam, Department of Medical Microbiology and Infection prevention, Laboratory of Experimental Virology, Amsterdam, the Netherlands.ORCID http://orcid.org/0000-0003-4493-7885
Gius KersterAmsterdam UMC, University of Amsterdam, Department of Medical Microbiology and Infection prevention, Laboratory of Experimental Virology, Amsterdam, the Netherlands.
Barbera D C van SchaikBioinformatics 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.
Aldo JongejanBioinformatics 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.ORCID http://orcid.org/0000-0002-8948-2549
Angela I SchriekAmsterdam UMC, University of Amsterdam, Department of Medical Microbiology and Infection prevention, Laboratory of Experimental Virology, Amsterdam, the Netherlands.
Marloes GrobbenAmsterdam UMC, University of Amsterdam, Department of Medical Microbiology and Infection prevention, Laboratory of Experimental Virology, Amsterdam, the Netherlands.ORCID http://orcid.org/0000-0002-1559-9592
Philip J M BrouwerAmsterdam UMC, University of Amsterdam, Department of Medical Microbiology and Infection prevention, Laboratory of Experimental Virology, Amsterdam, the Netherlands.
Karlijn van der StratenAmsterdam UMC, University of Amsterdam, Department of Medical Microbiology and Infection prevention, Laboratory of Experimental Virology, Amsterdam, the Netherlands.ORCID http://orcid.org/0000-0001-6373-9302
Yoann AldonAmsterdam UMC, University of Amsterdam, Department of Medical Microbiology and Infection prevention, Laboratory of Experimental Virology, Amsterdam, the Netherlands.ORCID http://orcid.org/0000-0001-9831-9391
Joan Capella-PujolAmsterdam UMC, University of Amsterdam, Department of Medical Microbiology and Infection prevention, Laboratory of Experimental Virology, Amsterdam, the Netherlands.ORCID http://orcid.org/0000-0002-7375-7958
Jonne L SnitselaarAmsterdam UMC, University of Amsterdam, Department of Medical Microbiology and Infection prevention, Laboratory of Experimental Virology, Amsterdam, the Netherlands.
Wouter OlijhoekAmsterdam UMC, University of Amsterdam, Department of Medical Microbiology and Infection prevention, Laboratory of Experimental Virology, Amsterdam, the Netherlands.
Aafke AartseAmsterdam UMC, University of Amsterdam, Department of Medical Microbiology and Infection prevention, Laboratory of Experimental Virology, Amsterdam, the Netherlands.
Mitch BrinkkemperAmsterdam UMC, University of Amsterdam, Department of Medical Microbiology and Infection prevention, Laboratory of Experimental Virology, Amsterdam, the Netherlands.
Ilja BontjerAmsterdam UMC, University of Amsterdam, Department of Medical Microbiology and Infection prevention, Laboratory of Experimental Virology, Amsterdam, the Netherlands.ORCID http://orcid.org/0000-0002-8406-7733
Judith A BurgerAmsterdam UMC, University of Amsterdam, Department of Medical Microbiology and Infection prevention, Laboratory of Experimental Virology, Amsterdam, the Netherlands.
Meliawati PonimanAmsterdam UMC, University of Amsterdam, Department of Medical Microbiology and Infection prevention, Laboratory of Experimental Virology, Amsterdam, the Netherlands.
Tom P L BijlAmsterdam UMC, University of Amsterdam, Department of Medical Microbiology and Infection prevention, Laboratory of Experimental Virology, Amsterdam, the Netherlands.
Jonathan L TorresDepartment of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA, 92037, USA.ORCID http://orcid.org/0000-0003-0137-8497
Jeffrey CoppsDepartment of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA, 92037, USA.ORCID http://orcid.org/0000-0003-4793-7258
Isabel Cuella MartinAmsterdam UMC, University of Amsterdam, Department of Medical Microbiology and Infection prevention, Laboratory of Experimental Virology, Amsterdam, the Netherlands.ORCID http://orcid.org/0000-0001-7543-3386
Steven W de TaeyeAmsterdam UMC, University of Amsterdam, Department of Medical Microbiology and Infection prevention, Laboratory of Experimental Virology, Amsterdam, the Netherlands.
Godelieve J de BreeDepartment of Internal Medicine, Amsterdam UMC, University of Amsterdam, Amsterdam Institute for Infection and Immunity, Amsterdam Institute for Infection and Immunity, Amsterdam, the Netherlands.
Andrew B WardDepartment of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA, 92037, USA.ORCID http://orcid.org/0000-0001-7153-3769
Kwinten SliepenAmsterdam UMC, University of Amsterdam, Department of Medical Microbiology and Infection prevention, Laboratory of Experimental Virology, Amsterdam, the Netherlands.ORCID http://orcid.org/0000-0003-1414-0648
Antoine H C van KampenBioinformatics 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.
Perry D MoerlandBioinformatics 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.ORCID http://orcid.org/0000-0002-2357-3659
Rogier W SandersAmsterdam UMC, University of Amsterdam, Department of Medical Microbiology and Infection prevention, Laboratory of Experimental Virology, Amsterdam, the Netherlands. r.w.sanders@amsterdamumc.nl.ORCID http://orcid.org/0000-0002-2324-8573
Marit J van GilsAmsterdam UMC, University of Amsterdam, Department of Medical Microbiology and Infection prevention, Laboratory of Experimental Virology, Amsterdam, the Netherlands. m.j.vangils@amsterdamumc.nl.ORCID http://orcid.org/0000-0003-3422-8161
Amsterdam University Medical Centers · NLScripps Research Institute · USAmsterdam Neuroscience · NLBiomedical Primate Research Centre · NLCornell University · US
Funding
No grant is acknowledged in the PubMed record.
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.
Indexed as
COVID-19SARS-CoV-2Antibodies, NeutralizingAntibodies, ViralCOVID-19 VaccinesEpitopesHumansImmunoglobulin IsotypesReceptors, Antigen, B-CellSpike Glycoprotein, CoronavirusAntibodies, NeutralizingAntibodies, ViralCOVID-19 VaccinesEpitopesImmunoglobulin IsotypesReceptors, Antigen, B-CellSpike Glycoprotein, Coronavirusspike protein, SARS-CoV-2
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