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

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.