Trypanosoma cruzi 's 80 kDa Prolyl oligopeptidase(Tc80) confers protection against Chagas disease

Abstract

Chagas disease is a chronic parasitosis caused by the protozoan Trypanosoma cruzi that affects about 8 million people over the world. Current etiological treatments have several limitations, and indeed, prophylactic or therapeutic vaccines have emerged as an interesting control strategy. In this work, we proposed T. cruzi 80 kDa prolyl oligopeptidase (Tc80), as a new antigen for vaccines against Chagas? disease. This protein is a secreted protease expressed by all parasite stages and it is involved in extracellular matrix degradation and host-cell invasion.We designed different vaccine approaches including Tc80 recombinant protein and Tc80-coding gene using a bacterial vector as DNA delivery system. Immunized mice developed Tc80-specific antibodies which were able to carry out different functions such as: enzymatic inhibition, parasite invasion blocking and complement-mediated lysis of trypomastigotes. Furthermore, vaccinated mice elicited strong cell-mediated immunity. Spleen cells from immunized mice proliferated and secreted Th1 cytokines (IL-2, IFN-γ and TNF-α) upon re-stimulation with rTc80. Moreover, we found Tc80-specific polyfunctional CD4 T cells, and cytotoxic T cell activity against a Tc80 MHC-I peptide.Immunization protocols were able to confer protection against T. cruzi infection. After a lethal challenge, immunized mice showed decreased parasitemia and higher survival rate compared to non-immunized control mice. Moreover, in a chronic infection model, we found that immunized mice presented reduced levels of myopathy-linked enzymes, electrocardiographic disorders and lower parasite burden and inflammatory cells in target tissues than control group.The immunogenicity and protection-conferring ability of Tc80-based vaccines make this molecule a proper immunogen for a mono or multicomponent vaccine against Chagas disease.