Abstrakt

Introduction Infection with the ubiquitous parasite Toxoplasma gondii is a threat for immunocompro- mised patients and pregnant women and effective immune-prophylaxis is still lacking. Methods Here we tested a mixture of recombinant T . gondii antigens expressed in different develop- mental stages, i.e., SAG1, MAG1 and GRA7 (SMG), and a lysate derived from T . gondii tachyzoites (TLA) for prophylactic vaccination against cyst formation. Both vaccine formula- tions were applied systemically followed by an oral TLA-booster in BALB/c mice. Results Systemic priming with SMG and oral TLA-booster did not show significant induction of pro- tective immune responses. In contrast, systemic priming and oral booster with TLA induced higher levels of Toxoplasma -specific IgG, IgG1 and IgG2a in sera as well as high levels of Toxoplasma -specific IgG1 in small intestines. Furthermore, high levels of Toxoplasma-spe- cific Th1-, Th17- and Th2-associated cytokines were only detected in restimulated spleno- cytes of TLA-vaccinated mice. Importantly, in mice orally infected with T . gondii oocysts, only TLA-vaccination and booster reduced brain cysts. Furthermore, sera from these mice reduced tachyzoites invasion of Vero cells in vitro , indicating that antibodies may play a criti- cal role for protection against Toxoplasma infection. Additionally, supernatants fromsplenocyte cultures of TLA-vaccinated mice containing high levels of IFN- γ lead to substan- tial production of nitric oxide (NO) after incubation with macrophages in vitro . Since NO is in- volved in the control of parasite growth, the high levels of IFN- γ induced by vaccination with TLA may contribute to the protection against T . gondii . Conclusion In conclusion, our data indicate that prime-boost approach with TLA, but not with the mixture of recombinant antigens SMG, induces effective humoral and cellular Toxoplasma -specific responses and leads to significant reduction of cerebral cysts, thereby presenting a viable strategy for further vaccine development against T . gondii infection.

Cytowania

Autorzy (8)