Immunotherapy of TSA-1.C4 or in combination with BNZ confers protection against Trypanosoma cruzi infection with a distinct cytokine response.

Abstract

Chagas disease is a poverty-related neglected tropical disease caused by the protozoan Trypanosoma cruzi affecting approximately 6.3 million people, predominantly in the Americas. Approximately 30% of T. cruzi infections progress to chronic cardiomyopathy and 10% of these cases end in death from cardiac failure. The first-line drug Benznidazole (BNZ) require a prolonged treatment regimen and can be highly toxic. Here, we evaluate a therapeutic vaccine in T. cruzi-infected mice, based on the recombinant Trypomastigote Surface Antigen 1 (TSA-1.C4) protein and the emulsified adjuvant E6020, and in combination with a suboptimal dose of BNZ. We observed a reduced burden parasite in blood in mice receiving either with TSA-1.C4 vaccine alone or in combination with a low dose of BNZ. TSA-1.C4-specific IgG and isotype levels were increased in all experimental groups receiving TSA-1.C4 protein treatment, confirming its immunogenicity. Mice treated with TSA-1.C4 vaccine in combination with BNZ exhibit a reduced cardiac inflammation as well as an antigen-specific IFN-γ CD4T cells with an IL-2 and IL-4 cytokine production. Even though TSA-1.C4 vaccine alone induced a cytokine response by IFN-γ and IL-10 production, only the TSA-1.C4 vaccine plus BNZ reduced cardiac inflammatory infiltrate compared to infected untreated mice. In conclusion the therapeutic vaccine with a low dose of BNZ prevent cardiac inflammation and provide a balanced Th1/Th2 cytokine immune response in a murine model of acute Chagas disease.