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

Abstract Despite the availability of effective vaccines, pneumococcal disease remains a major global health concern. Pneumococcal vaccines are multivalent vaccines that have progressively increased in valency, a change associated with lower antibody titers to individual polysaccharide antigens. Whether increasing vaccine valency influences B cell responses through antigenic competition remains incompletely understood. Here, we studied pneumococcal polysaccharide-specific B cell responses in peripheral blood and lymph nodes of healthy adults following vaccination with the 13-valent pneumococcal conjugate vaccine. Antigen-specific memory B cells in peripheral blood expanded 2 weeks post-vaccination, whereas germinal center formation was delayed and peaked after 4 weeks. Notably, germinal center B cell responses were dominated by a limited number of specificities, in contrast to the more evenly distributed expansion observed in peripheral blood. Together, these data highlight the importance of extrafollicular responses in adult anti-pneumococcal polysaccharide immunity and provide evidence for antigenic competition during lymph node germinal center formation, which may have important implications in the context of multivalent vaccines. Summary Using lymph node fine needle aspiration, the study characterizes germinal center responses to multivalent pneumococcal conjugate vaccines. Antigen-specific peripheral blood B cells expand before germinal center formation, and germinal center B cells display a restricted serotype-specific response.