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Clinical Research and Public HealthIn-Press PreviewImmunologyInfectious disease Open Access | 10.1172/jci.insight.209784

The human germinal center B cell response to pneumococcal conjugate vaccines is antigenically restricted

David W. de Vos,1 Marina Johnson,2 Dennis Hoving,1 Giovanni E. Loe-Sack-Sioe,1 Catherina Kienhuis,1 Els L. van Persijn van Meerten,3 David Goldblatt,2 Leo G. Visser,1 Anna H.E. Roukens,1 and Simon P. Jochems1

1Leiden University Center for Infectious Diseases, Leiden University Medical Center, Leiden, Netherlands

2Infection, Immunity and Inflammation Department, UCL Great Ormond Street Institute of Child Health, Biomedical Research Centre, London, United Kingdom

3Department of Radiology, Leiden University Medical Center, Leiden, Netherlands

Find articles by de Vos, D. in: PubMed | Google Scholar

1Leiden University Center for Infectious Diseases, Leiden University Medical Center, Leiden, Netherlands

2Infection, Immunity and Inflammation Department, UCL Great Ormond Street Institute of Child Health, Biomedical Research Centre, London, United Kingdom

3Department of Radiology, Leiden University Medical Center, Leiden, Netherlands

Find articles by Johnson, M. in: PubMed | Google Scholar

1Leiden University Center for Infectious Diseases, Leiden University Medical Center, Leiden, Netherlands

2Infection, Immunity and Inflammation Department, UCL Great Ormond Street Institute of Child Health, Biomedical Research Centre, London, United Kingdom

3Department of Radiology, Leiden University Medical Center, Leiden, Netherlands

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1Leiden University Center for Infectious Diseases, Leiden University Medical Center, Leiden, Netherlands

2Infection, Immunity and Inflammation Department, UCL Great Ormond Street Institute of Child Health, Biomedical Research Centre, London, United Kingdom

3Department of Radiology, Leiden University Medical Center, Leiden, Netherlands

Find articles by Loe-Sack-Sioe, G. in: PubMed | Google Scholar

1Leiden University Center for Infectious Diseases, Leiden University Medical Center, Leiden, Netherlands

2Infection, Immunity and Inflammation Department, UCL Great Ormond Street Institute of Child Health, Biomedical Research Centre, London, United Kingdom

3Department of Radiology, Leiden University Medical Center, Leiden, Netherlands

Find articles by Kienhuis, C. in: PubMed | Google Scholar

1Leiden University Center for Infectious Diseases, Leiden University Medical Center, Leiden, Netherlands

2Infection, Immunity and Inflammation Department, UCL Great Ormond Street Institute of Child Health, Biomedical Research Centre, London, United Kingdom

3Department of Radiology, Leiden University Medical Center, Leiden, Netherlands

Find articles by van Persijn van Meerten, E. in: PubMed | Google Scholar

1Leiden University Center for Infectious Diseases, Leiden University Medical Center, Leiden, Netherlands

2Infection, Immunity and Inflammation Department, UCL Great Ormond Street Institute of Child Health, Biomedical Research Centre, London, United Kingdom

3Department of Radiology, Leiden University Medical Center, Leiden, Netherlands

Find articles by Goldblatt, D. in: PubMed | Google Scholar

1Leiden University Center for Infectious Diseases, Leiden University Medical Center, Leiden, Netherlands

2Infection, Immunity and Inflammation Department, UCL Great Ormond Street Institute of Child Health, Biomedical Research Centre, London, United Kingdom

3Department of Radiology, Leiden University Medical Center, Leiden, Netherlands

Find articles by Visser, L. in: PubMed | Google Scholar

1Leiden University Center for Infectious Diseases, Leiden University Medical Center, Leiden, Netherlands

2Infection, Immunity and Inflammation Department, UCL Great Ormond Street Institute of Child Health, Biomedical Research Centre, London, United Kingdom

3Department of Radiology, Leiden University Medical Center, Leiden, Netherlands

Find articles by Roukens, A. in: PubMed | Google Scholar |

1Leiden University Center for Infectious Diseases, Leiden University Medical Center, Leiden, Netherlands

2Infection, Immunity and Inflammation Department, UCL Great Ormond Street Institute of Child Health, Biomedical Research Centre, London, United Kingdom

3Department of Radiology, Leiden University Medical Center, Leiden, Netherlands

Find articles by Jochems, S. in: PubMed | Google Scholar |

Published October 22, 2026 - More info

JCI Insight. https://doi.org/10.1172/jci.insight.209784.
Copyright © 2026, de Vos et al. This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Published October 22, 2026 - Version history
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Abstract

BACKGROUND. Despite the availability of effective vaccines, pneumococcal disease remains a major global health concern. Pneumococcal conjugate vaccines (PCVs) have progressively increased in valency, a change associated with reduced antibody titers against individual polysaccharide antigens. Whether increasing vaccine valency affects B cell responses through antigenic competition remains incompletely understood. We investigated pneumococcal polysaccharide-specific B cell responses in peripheral blood and vaccine draining lymph nodes following vaccination with PCV13.

METHODS. Healthy adults (n = 5) received PCV13. Peripheral blood and lymph node fine needle aspirations (FNA) were collected longitudinally at baseline and after vaccination. Pneumococcal polysaccharide-specific B cell responses, polysaccharide-specific antibody responses and opsonophagocytic activity were analyzed in peripheral blood and draining lymph nodes.

RESULTS. Antigen-specific memory B cells in peripheral blood expanded rapidly and peaked 2 weeks after vaccination. In contrast, germinal center formation in lymph nodes was delayed, peaking at 4 weeks. Germinal center B cell responses were dominated by a limited number of polysaccharide specificities, whereas the expansion of memory B cells in peripheral blood was more evenly distributed across specificities. Polysaccharide-specific antibodies followed similar dynamics in plasma and FNA supernatant.

CONCLUSION. Adult immune responses to PCV are characterized by robust extrafollicular memory B cell expansion and delayed germinal center responses. The restricted specificity of germinal center B cells provides evidence for antigenic competition during germinal center formation, with potential implications for the design and immunogenicity of multivalent vaccines.

TRIAL REGISTRATION. EU CT number 2022-501519-15-00.

FUNDING. LUMC PhD Fellowship, ZonMW Vidi and ZonMW Clinical Fellowship.

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