{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T16:39:28Z","timestamp":1792687168461,"version":"4.5.0"},"reference-count":0,"publisher":"American Society for Clinical Investigation","license":[{"start":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T00:00:00Z","timestamp":1792627200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"ZonMw","award":["09150172210056"],"award-info":[{"award-number":["09150172210056"]}]},{"name":"ZonMw","award":["09032212110032"],"award-info":[{"award-number":["09032212110032"]}]},{"name":"LUMC","award":["PhD fellowship"],"award-info":[{"award-number":["PhD fellowship"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:p>\n                    <jats:bold>BACKGROUND.<\/jats:bold>\n                    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.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>METHODS.<\/jats:bold>\n                    Healthy adults (\n                    <jats:italic>n<\/jats:italic>\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.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>RESULTS.<\/jats:bold>\n                    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.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>CONCLUSION.<\/jats:bold>\n                    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.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>TRIAL REGISTRATION.<\/jats:bold>\n                    EU CT number 2022-501519-15-00.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>FUNDING.<\/jats:bold>\n                    LUMC PhD Fellowship, ZonMW Vidi and ZonMW Clinical Fellowship.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.209784","type":"journal-article","created":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T16:00:38Z","timestamp":1792684838000},"source":"Crossref","is-referenced-by-count":0,"title":["The human germinal center B cell response to pneumococcal conjugate vaccines is antigenically restricted"],"prefix":"10.1172","author":[{"given":"David W.","family":"de Vos","sequence":"first","affiliation":[{"name":"Leiden University Center for Infectious Diseases, Leiden University Medical Center, Leiden, Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina","family":"Johnson","sequence":"additional","affiliation":[{"name":"Infection, Immunity and In\ufb02ammation Department, UCL Great Ormond Street Institute of Child Health, Biomedical Research Centre, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9246-5774","authenticated-orcid":true,"given":"Dennis","family":"Hoving","sequence":"additional","affiliation":[{"name":"Leiden University Center for Infectious Diseases, Leiden University Medical Center, Leiden, Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanni E.","family":"Loe-Sack-Sioe","sequence":"additional","affiliation":[{"name":"Leiden University Center for Infectious Diseases, Leiden University Medical Center, Leiden, Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherina","family":"Kienhuis","sequence":"additional","affiliation":[{"name":"Leiden University Center for Infectious Diseases, Leiden University Medical Center, Leiden, Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Els L.","family":"van Persijn van Meerten","sequence":"additional","affiliation":[{"name":"Department of Radiology, Leiden University Medical Center, Leiden, Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Goldblatt","sequence":"additional","affiliation":[{"name":"Infection, Immunity and In\ufb02ammation Department, UCL Great Ormond Street Institute of Child Health, Biomedical Research Centre, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leo G.","family":"Visser","sequence":"additional","affiliation":[{"name":"Leiden University Center for Infectious Diseases, Leiden University Medical Center, Leiden, Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1397-0992","authenticated-orcid":true,"given":"Anna H.E.","family":"Roukens","sequence":"additional","affiliation":[{"name":"Leiden University Center for Infectious Diseases, Leiden University Medical Center, Leiden, Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4835-1032","authenticated-orcid":true,"given":"Simon P.","family":"Jochems","sequence":"additional","affiliation":[{"name":"Leiden University Center for Infectious Diseases, Leiden University Medical Center, Leiden, Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"232","published-online":{"date-parts":[[2026,10,22]]},"container-title":["JCI Insight"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/insight.jci.org\/articles\/view\/209784\/files\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T16:00:40Z","timestamp":1792684840000},"score":1,"resource":{"primary":{"URL":"http:\/\/insight.jci.org\/articles\/view\/209784"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,22]]},"references-count":0,"alternative-id":["10.1172\/jci.insight.209784"],"URL":"https:\/\/doi.org\/10.1172\/jci.insight.209784","relation":{},"ISSN":["2379-3708"],"issn-type":[{"value":"2379-3708","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,22]]}}}