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Identifying novel therapeutic targets for Chagas disease is a scientific priority. Recently, Hossain et al. used an innovative metabolomic approach to define disease tolerance mechanisms and identify therapeutic targets for Chagas disease. This is the first study translating metabolomic data to develop novel treatments for Chagas disease. [ABSTRACT FROM AUTHOR]

• The recombinant multi-epitope Tc24-C4.10E reduces parasitemia peak in acute T. cruzi infected mice. • The recombinant multi-epitope Tc24-C4.10E elicit an antigen-specific CD8 + T cell response producing IFNγ and IL-4 cytokines. • This is the first approach using as scaffold a recombinant protein to fuse 10 CD8 + T. cruzi epitopes. About 6.5 million people worldwide are afflicted by Chagas disease, which is caused by the protozoan parasite Trypanosoma cruzi. The development of a therapeutic vaccine to prevent the progression of Chagasic cardiomyopathy has been proposed as an alternative for antiparasitic chemotherapy. Bioinformatics tools can predict MHC class I CD8 + epitopes for inclusion in a single recombinant protein with the goal to develop a multivalent vaccine. We expressed a novel recombinant protein Tc24-C4.10E harboring ten nonameric CD8 + epitopes and using Tc24-C4 protein as scaffold to evaluate the therapeutic effect in acute T. cruzi infection. T. cruzi -infected mice were immunized with Tc24-C4.10E or Tc24-C4 in a 50-day model of acute infection. Tc24-C4.10E-treated mice showed a decreased parasitemia compared to the Tc24-C4 (non-adjuvant) immunized mice or control group. Moreover, Tc24-C4.10E induced a higher stimulation index of CD8 + T cells producing IFNγ and IL-4 cytokines. These results suggest that the addition of the MHC Class I epitopes to Tc24-C4 can synergize the antigen-specific cellular immune responses, providing proof-of-concept that this approach could lead to the development of a promising vaccine candidate for Chagas disease. [ABSTRACT FROM AUTHOR]