Serotype 33F is an emerging Streptococcus pneumoniae (Spn) serotype associated with asymptomatic nasopharyngeal (NP) colonization and invasive pneumococcal disease (IPD). Serotype 33F is a component in the advanced version of the pneumococcal conjugate vaccine 15 (PCV 15) formulation. However, in the murine vaccination model, serotype 33F exhibits reduced immunogenicity, correlating with reduced protection against 33F. To investigate if the reduced immunogenic potential of serotype 33F can be overcome by optimizing the vaccine dosing, we immunized C57BL/6 mice with a range of CRM conjugated monovalent 33F dosages, i.e., 0.04 - -0.32 μg. Our data show the dose-dependent differences in 33F vaccine responses with a higher immunization dose (0.32 μg) producing significantly higher levels of serum antibody responses, correlating with enhanced in vivo protection against Spn bacterial colonization. Our findings suggest that higher immunization dosing can overcome the inherently reduced immunogenicity of emerging 33F Spn serotype.
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