In vivo evaluation of new adjuvant systems based on combination of Salmonella Typhi porins with particulate systems: Liposomes versus polymeric particles.

Subunit vaccines that have weak immunogenic activity require adjuvant systems for enhancedcellular and long-acting humoral immune responses. Both lipid-based and polymeric-based particulate adjuvants have been widely investigated to induce the desired immune responses against the subunit vaccines. The adjuvant efficacy of these particulate adjuvants depends upon their physicochemical properties such as particle size, surface charge, shape and their composition. Previously, we showed in vitro effect of adjuvant systems based on combination of chitosan and Salmonella Typhi porins in microparticle or nanoparticle form, which were spherical with positive surface charge. In the present study, we have further developed an adjuvant system based on combination of porins with liposomes (cationic and neutral) and investigated the adjuvant effect of both the liposomal and polymeric systems in BALB/c mice using a model antigen, ovalbumin. Humoral immune responses were determined following priming and booster dose at 15-day intervals. In overall, IgM and IgG levels were induced in the presence of both the liposomal and polymeric adjuvant systems indicating the positive impact of combination with porins. The highest IgM levels were obtained on Day 8, and liposomal adjuvant systems were found to elicit significantly higher IgM levels compared to polymeric systems. IgG levels were increased significantly after booster, particularly more profound with the micro-sized polymeric system when compared to cationic liposomal system with nano-size. Our results demonstrated that the developed particulate systems are promising both as an adjuvant and delivery system, providing enhanced immune responses against subunit antigens, and have the potential for long-term protection.

Development of multistage recombinant protein vaccine formulations against toxoplasmosis using a new chitosan and porin based adjuvant system.

Toxoplasmosis is a global health problem affecting both human and animal populations. The lack of effective treatment makes the development of a vaccine against toxoplasmosis one of the main goals in the management of this disease. In our study, vaccine formulations containing the multistage recombinant antigens, rBAG1 + rGRA1 were developed with a combined adjuvant system consisting of chitosan and Salmonella Typhi porins in micro (MicroAS) and nanoparticulate (NanoAS) forms. BALB/c mice were immunized intraperitoneally with vaccine formulations two times at three-week intervals. Three weeks after the second vaccination, mice were challenged with 7-8 live tissue cysts of the virulent T. gondii PRU strain by oral gavage. Higher cellular uptake by macrophages and enhanced cellular (IFN-γ and I-4 in stimulated spleen cells) and humoral (IgG, IgG1, IgG2a) responses were obtained with the adjuvanted formulation, higher with microsystem when compared to that of nanosystem. Microsystem was found to stimulate Th1-polarized immune responses, whereasnon-adjuvanted antigens stimulated Th2-polarized immune response. The highest survival rate and reduction in cysts numbers and T. gondii DNA were obtained with the adjuvanted antigens.Our study showed that adjuvanted multistage recombinant vaccine systems increase theimmune response with strong protection againstT. gondii, more profoundly in microparticulate form.