Cell-Mediated and Humoral Immune Responses to Bordetella pertussis Inactivated Whole-Cells Encapsulated Alginate Microspheres as a New Vaccine Candidate

Background: Effectiveness of the whole-cell pertussis vaccine is apparent, but improvement in the quality of the vaccine is necessary to achieve strong immunogenicity with a low bacterial number content. Method: Inactivated Bordetella pertussis (B. pertussis) cells entrapped microspheres were prepared via an emulsification method and analyzed for morphology, size, size distribution, loading efficiency, loading capacity, release kinetic, in vivo cytokines and antigen specific antibody subclasses. Results: Bordetella pertussis encapsulated microspheres exhibited a smooth surface and spherical shape, mean particle size 151.1 mu m, size distribution index 0.43, loading efficiency 89.6%, loading capacity 36.3% and release kinetic similar to the Korsmeyer-Peppas model. Splenocytes of animals immunized with new microsphere-based whole-cell vaccine produced greater quantities of IFN-gamma and higher amounts of IL-4 and IL-5 cytokines compared to conventional adjuvant-adsorbed vaccines. Conventional adjuvant-adsorbed vaccines produced smaller quantities of IL-4 and IL-5. Bordetella pertussis entrapped microspheres induced both cell-mediated and humoral antibody in mice, evidenced by high levels of IgG2a and IgG1. IgG2a levels in mice were enhanced using the common aluminum phosphate-adsorbed B. pertussis whole-cell vaccine, and IgG1 levels did not increase significantly. Bordetella pertussis entrapped microspheres and common B. pertussis whole-cell vaccine samples enhanced total IgG levels in mice; however, B. pertussis-entrapped microspheres produced significantly higher levels of total IgG than other test samples. Conclusion: Encapsulation of inactive B. pertussis cells in microspheres appears to be a suitable approach for improving the wP vaccine quality, in particular by decreasing its toxicity to obtain good cell-mediated and humoral immunogenicity with a low bacterial number content.