JCI insight · 2026
The human germinal center B cell response to pneumococcal conjugate vaccines is antigenically restricted.
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de Vos David W, Johnson Marina, Hoving Dennis, Loe-Sack-Sioe Giovanni E, Kienhuis Catherina, van Persijn van Meerten Els L, Goldblatt David, Visser Leo G, Roukens Anna He, Jochems Simon P
Аннотация
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.
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.