Dados do Trabalho

Título

A recombinant chimeric protein-based vaccine combined with distinct adjuvants, induces immunogenicity and protection against Leishmania infantum infection

Introdução

Visceral leishmaniasis (VL) is a disease that affects thousands of people worldwide and is potentially fatal when untreated. Available treatments present problems due to drug toxicity, administration period, and high cost. Diagnosis is difficult due to the variable sensitivity and/or specificity of tests, which increases the difficulty in controlling the spread of the disease. In addition, the control measures provided by government institutions have various failures, which makes prophylactic vaccination a good alternative for reducing the high number of disease cases.

Objetivo (s)

The aim of this study was developing a recombinant chimeric protein based on T-cell epitopes identified from the immunogenic Leishmania amastigote proteins LiHyp1, LiHyV, LiHyC and LiHyG (ChimT) and evaluate their immunogenicity and protective efficacy as a vaccine when associated with the adjuvants saponin (Sap) or monophosphoryl lipid A (MPLA).

Material e Métodos

BALB/c mice were vaccinated with 20 μg of ChimT alone or associated with 20 μg of Sap or MPLA. In addition, control animals received 20 μg of Sap, MPLA or saline only. The animals received three doses of the products, which were administered at 14-day intervals, and 30 days after the last dose, part of them were euthanized and their spleens and sera were collected for immunological assays. At the same time, the remaining animals were infected with 10^7 L. infantum stationary promastigotes, and 45 days post-infection they were euthanized and their organs and sera were collected for immunological and parasitological assays.

Resultados e Conclusão

ChimT/Sap and ChimT/MPLA induced a specific Th1-type immune response, characterized by high levels of IFN-γ, IL-2, IL-12, TNF-α and GM-CSF cytokines and low production of anti-leishmanial IL-4 and IL-10 cytokines. Significantly increased levels of nitrite and parasite-specific IgG2a isotype antibodies were also detected in stimulated spleen cell cultures from immunized and infected mice. Significant reductions in the parasite load in the internal organs of the immunized and infected mice correlated with the immunological findings. ChimT/MPLA showed marginally superior immunogenicity than ChimT/Sap, being a better formulation due to transient edema induced by ChimT/Sap at the inoculation site. In conclusion, the chimeric protein administered with adjuvants appears to be a promising vaccine candidate to protect against VL.

Palavras-chave

visceral leishmaniasis; vaccine; chimeric protein; Th1 adjuvants

Agradecimentos

CAPES; CNPq; FAPEMIG; PPGIMT