Recombinant protein vaccines are safe but elicit low immunological responses. The new generation of adjuvants is currently reversing this situation. Here, a new
antigen-adjuvant combination for protection against experimental
Chagas disease was assessed. The
antigen used in the formulation was a glycosylated mutant inactive
trans-sialidase (mTS) that was previously proven to be highly protective against
Trypanosoma cruzi infection; here, we show that it can be produced in large quantities and high quality using Pichia pastoris. The adjuvant used in the formulation was
ISCOMATRIX (IMX), which was found to be effective and safe in human clinical trials of
vaccines designed to control other intracellular
infections. Fifteen days after the third immunization, mice immunized with mTS-IMX showed a TS-specific
IgG response with titers >10(6) and high avidity, an increased
IgG2a/
IgG1 ratio, significant delayed-type
hypersensitivity (DTH) reactivity, a balanced production of IFN-γ and
IL-10 by splenocytes and a strong IFN-γ secretion by CD8(+) T lymphocytes. When these mice where challenged with 1000 trypomastigotes of T. cruzi, all mTS-IMX immunized mice survived, whereas mice immunized with mTS alone, IMX or PBS exhibited high mortality. Remarkably, during acute
infection, when the
parasitemia is highest in this
infection model (day 21), mTS-IMX immunized mice had ∼50 times less
parasitemia than non-immunized mice. At this moment and also in the chronic phase, 100 days after
infection, tissue presented ∼4.5 times lower parasite load and associated inflammatory infiltrate and lesions. These results indicate that protection against
Chagas disease can be achieved by a
protein antigen-adjuvant mTS formulation that is compatible with human medicine. Therefore, the current formulation is a highly promising T. cruzi
vaccine candidate to be tested in clinical trials.