Toksoplazmozise karşı rekombinant protein antijenleri içeren yeni bir adjuvant sistemi ile aşı geliştirilmesi

Abstract

Toxoplasmosis is a global health problem affecting human and animal populations. Currently, there is no effective treatment for the infection. For strong protection against toxoplasmosis, there is still a need for a vaccine which is effective on different stages of the parasite's life cycle. Recombinant protein vaccines have been investigated for this purpose. In this thesis, it was aimed to develop a vaccine formulation with enhanced efficacy and protection by using combination of recombinant BAG1 and GRA1 proteins incorporated with our developed micro- and nanoparticulate adjuvant systems, based on combination of chitosan and Salmonella Typhi porins. After characterization of the developed vaccine systems, immunization and protection studies were performed in BALB/c mice. Following two vaccinations with 21 day-intervals, cellular (IFN- and IL-4) and humoral responses (IgG, IgG1, IgG2a) were examined. Three weeks after the second vaccination, mice were infected with 7-8 live tissue cysts of the virulent T. gondii PRU strain by oral gavage. In presence of adjuvant, increased cellular uptake by macrophages, enhanced cellular (IFN- and IL-4) and humoral (IgG, IgG1, IgG2a) responses and high protection were obtained. The highest efficacy and protection were obtained with the microparticulate adjuvant system when compared to nanoparticulate adjuvant system. The combination of the recombinant proteins was found to induce Th2-bias immune responses, whilst in presence of adjuvant systems, Th1-bias immune responses were induced. In this thesis, it has been shown that a successful vaccine system was developed in presence of the newly developed adjuvant system resulting in enhanced immune responses against T. gondii with high protectivity.