In this study， a recombinant chimeric protein (RCP)， which was composed of specific CD4 and CD8 T-cell epitopes to murine and human haplotypes， was evaluated as an immunogen against Leishmania infantum infection in a murine model. BALB/c mice received saline were immunized with saponin or with RCP with or without an adjuvant. The results showed that RCP/saponin-vaccinated mice presented significantly higher levels of antileishmanial IFN-γ， IL-12 and GM-CSF before and after challenge， which were associated with the reduction of IL-4 and IL-10 mediated responses. These animals showed significant reductions in the parasite burden in all evaluated organs， when both limiting dilution and quantitative real-time PCR techniques were used. In addition， the protected animals presented higher levels of parasite-specific nitrite， as well as the presence of anti-Leishmania IgG2a isotype antibodies. In conclusion， the RCP/saponin vaccine could be considered as a prophylactic alternative to prevent against VL.