At the pre-booster timepoint, 87.5–91.3% of PHiD-CV/dPly/PhtD recipients and 97.5% of PHiD-CV recipients were seropositive. Post-booster, seropositivity rates increased to 97.6–100% of toddlers. Anti-PD antibody GMCs increased from pre- to post-primary vaccination and from pre- to post-booster for all PD-containing formulations (Table 3A). Four investigational vaccine formulations containing dPly and PhtD, with or without PS-conjugates, showed a similar safety

and reactogenicity profile to that of PHiD-CV in toddlers. No statistically significant difference was detected 17-AAG molecular weight in the incidence of grade 3 fever following at least one primary vaccine this website dose between the investigational vaccines and PHiD-CV, confirming the primary objective. Reactogenicity of the investigational vaccines did not appear to be dose-dependent. All dPly/PhtD-containing vaccines induced robust anti-protein

immune responses following primary and booster vaccination. The protein-only formulations tended to be more immunogenic than the formulations combining the proteins with PS-conjugates, both in primary and booster vaccination. As no immunological correlates of protection have yet been established for the pneumococcal proteins, the clinical relevance of this finding is not known. Addition of dPly and PhtD to the conjugate vaccine already formulations did not appear to have a negative effect on the immune response to the PS-conjugates. No clear trend for dose-dependency of the immune response was observed. Another study evaluating different PhtD-containing formulations showed a stronger immune response to the 25 μg dose than to the 6 μg dose, but no difference between the 25 and 100 μg doses [24]. Dose-related increases in immunogenicity were also observed for

other vaccine formulations containing 10 or 20 μg PhtD and pneumococcal choline-binding protein A (PcpA), with no further increase for the 50 μg dose [25], and for 10 and 25 μg doses of a dPly-containing vaccine, with no further increase for the 50 μg dose [26]. However, these studies involved adults whereas our study investigated toddlers, which could partially explain the difference in dose-dependency; toddlers have a less mature immune system which could result in a different immune response to vaccination. A different immune response in adults and toddlers was also observed in a study that characterized circulating antigen-specific CD4+ T cells responsive to six pneumococcal protein antigens (including PhtD and Ply). Adults had circulating memory CD4+ T cells that could be stimulated by all tested antigens, whereas young children had a more limited response with non-memory type antigen-specific T cells [27].