Chagas disease, caused by the protozoan parasite Trypanosoma cruzi is one of the most important neglected
parasitic diseases in the Americas.
Vaccines represent an attractive complementary strategy for the control of T. cruzi
infection and pre-clinical studies in mice demonstrated that trypomastigote
surface antigen (TSA-1) and the flagellar
calcium-binding (Tc24) parasite
antigens are promising candidates for
vaccine development. We performed here the first evaluation of the safety and immunogenicity of two
recombinant vaccine antigens (named TSA1-C4 and Tc24-C4) in naïve non-human primates. Three rhesus macaques received 3 doses of each
recombinant protein, formulated with E6020 (Eisai Co., Ltd.), a novel Toll-like receptor-4 agonist, in a stable
emulsion. All parameters from blood chemistry and blood cell counts were stable over the course of the study and unaffected by the
vaccine. A specific
IgG response against both
antigens was detectable after the first
vaccine dose, and increased with the second dose. After three
vaccine doses, stimulation of PBMCs with a
peptide pool derived from TSA1-C4 resulted in the induction of TSA1-C4-specific TNFα-, IL-2- and IFNγ-producing CD4+ in one or two animals while stimulation with a
peptide pool derived from
Tc24-C4 only activated IFNγ-producing CD4+T cells in one animal. In two animals there was also activation of TSA1-C4-specific IL2-producing CD8+ T cells. This is the first report of the immunogenicity of T. cruzi-derived recombinant
antigens formulated as an
emulsion with a TLR4 agonist in a non-human primate model. Our results strongly support the need for further evaluation of the preventive efficacy of this type of
vaccine in non-human primates and explore the effect of the
vaccine in a therapeutic model of naturally-infected Chagasic non-human primates, which would strengthen the rationale for the clinical development as a human
vaccine against
Chagas disease.