Combined prime-boost immunization with systemic and mucosal pneumococcal vaccines based on Pneumococcal surface protein A to enhance protection against lethal pneumococcal infections.

Limited protective effects of commercially available vaccines necessitate the development of novel pneumococcal vaccines. We recently reported a pneumococcal systemic vaccine containing two proteins, Pneumococcal surface protein A (PspA of family 1 and 2) and a bacterium-like particle-based pneumococcal mucosal vaccine containing PspA2 and PspA4 fragments, both eliciting broad protective immune responses. We had previously reported that subcutaneous (s.c.+s.c.+s.c.) immunization with the systemic vaccine induced more pronounced humoral serum IgG responses, while intranasal (i.n.+i.n.+i.n.) immunization with the mucosal vaccine elicited a more pronounced mucosal secretory IgA (sIgA) response. We hypothesized that a combinatorial administration of the two vaccines might elicit more pronounced and broader protective immune responses. Therefore, this study aimed to determine the efficacy of combinatorial prime-boost immunization using both systemic and mucosal vaccines for a pneumococcal infection. Combinatorial prime-boost immunization (s.c.+i.n. and i.n.+s.c.) induced not only IgG, but also mucosal sIgA production at high levels. Systemic priming and mucosal boosting immunization (s.c.+i.n.) provided markedly better protection than homologous prime-boost immunization (s.c.+s.c.+s.c. and i.n.+i.n.+i.n.). Moreover, it induced more robust Th1 and Th17 cell-mediated immune responses than mucosal priming and systemic boosting immunization (i.n.+s.c.). These results indicate that combinatorial prime-boost immunization potentially induces a robust systemic and mucosal immune response, making it an optimal alternative for maximum protection against lethal pneumococcal infections.