Study On Combined Prime-boost Immunization Of PspA Protein Vaccine And Experimental Method Of Adhesion Inhibition Of PspA Antibody

Limited protective effects of commercially available vaccines necessitate the development of novel pneumococcal vaccines.We recently reported a pneumococcal systemic vaccine containing two proteins,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 previously reported that subcutaneous immunization with the systemic vaccine induced more pronounced humoral serum IgG responses,while intranasal immunization with the mucosal vaccine elicited more pronounced mucosal secretory IgA(sIgA)responses.We hypothesized that combinatorial administration of the two vaccines would elicit more pronounced and broader protective immune responses.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 induced not only IgG but also mucosal sIgA production at high levels,which effectively cleared streptococcus pneumoniae from the lungs.Systemic priming and mucosal boosting immunization provided markedly better protection than homologous prime-boost immunization,and induced more robust Th1 and Th17 cell-mediated immune responses than mucosal priming and systemic boosting immunization.These results indicate that combinatorial prime-boost immunization potentially induces a robust systemic and mucosal immune response,and combinatorial systemic priming and mucosal boosting is an optimal alternative for maximum protection against lethal pneumococcal infections.The OPKA is an important tool for in vitro evaluation of pneumococcal polysaccharide vaccine.However,there is no effective evaluation method in vitro for the novel pneumococcal protein vaccine.We previously evaluated the effectiveness of PspA protein vaccine through passive immunization assay or complement inhibition assay,but the results were not satisfactory.Recent studies have reported that PspA plays an important role in the pneumococcal nasopharyngeal colonization.We believe that anti-PspA antibody may have important function of inhibiting bacterial adhesion.This study aimed to establish an adhesion inhibition assay against anti-PspA antibody and evaluated the effectiveness of PspA protein vaccine.The antibody serum could effectively inhibit the adhesion of different clade of strains,and the inhibition rate of all strains was greater than 50%.These results indicate that adhesion inhibition assay can be used as a basic reference for in vitro evaluation of pneumococcal protein vaccine,but the specific mechanism of this method needs to be further clarified in future studies.