Significant Variation in Serotype‐Specific Immunogenicity of the Seven‐ValentStreptococcus pneumoniaeCapsular Polysaccharide–CRM197Conjugate Vaccine Occurs Despite Vigorous T Cell Help Induced by the Carrier Protein

Streptococcus pneumoniae capsular polysaccharides (PnPSs) induce protective antibodies but are T cell-independent type 2 antigens and are poorly immunogenic in infants. Conjugate vaccines of PnPSs linked to proteins like cross-reactive material (CRM(197)) increase PS antibody titer and elicit immunologic memory in infants. Despite being linked to an identical carrier protein, each PS component of the 7-valent PnPS-CRM(197) vaccine has different immunogenicity. To determine whether variations in conjugate-induced memory T cell responses or PnPS-specific antibody-secreting cells (ASCs) were responsible for serotype-specific differences in immunogenicity, adults were immunized with 7-valent PnPS-CRM(197), and antibody titer, vaccine component-specific CD4(+) T cell recall response, numbers of PnPS-specific ASCs, and cytokine production were measured. PnPS-CRM(197) induced significantly different serotype-specific antibody titers, despite vigorous T cell recall responses to all 7 vaccine components, and production of interleukin (IL)-2, IL-5, IL-6, IL-10, and interferon-gamma. We conclude that PnPS-CRM(197) induces variable serotype-specific antibody titers, despite induction of comparable CRM(197)-specific memory T cell responses.