Leishmania LiHyC protein is immunogenic and induces protection against visceral leishmaniasis.

Abstract

Treatment against visceral leishmaniasis (VL) presents problems by the toxicity of drugs, high cost and/or emergence of resistant strains. The diagnosis is hampered by

variable sensitivity and/or specificity of tests. In this context, prophylactic vaccina- tion could represent a control measure against disease. In this study, the protective

efficacy of Leishmania LiHyC protein was evaluated in a murine model against Leish- mania infantum infection. LiHyC was used as recombinant protein (rLiHyC) associated

with saponin (rLiHyC/S) or Poloxamer 407-based polymeric micelles (rLiHyC/M) to immunize mice. Animals received also saline, saponin or empty micelles as controls. The immunogenicity was evaluated before and after the challenge, and results showed that vaccination with rLiHyC/S or rLiHyC/M induced the production of high levels of interferon-gamma (IFN-γ), interleukin (IL)-12 and granulocyte-macrophage

colony-stimulating factor in cell culture supernatants, as well as higher IFN-γ expres- sion evaluated by RT-qPCR and involvement from CD4+ and CD8+ T-cell subtypes

producing IFN-γ, tumor necrosis factor-α and IL-2. A positive lymphoproliferative response was also found in cell cultures from vaccinated animals, besides high levels of rLiHyC- and parasite-specific nitrite and IgG2a antibodies. Immunological assays correlated with significant reductions in the parasite load in the spleens, livers, bone marrows and draining lymph nodes from vaccinated mice, when compared to values found in the controls. The micellar composition showed slightly better immunological

and parasitological data, as compared to rLiHyC/S. Results suggest that rLiHyC asso- ciated with adjuvants could be considered for future studies as a vaccine candidate

against VL.