Dados do Trabalho

Título

Efficacy of an immunotherapy combining immunogenic chimeric protein plus adjuvant and amphotericin B against murine visceral leishmaniasis

Introdução

Visceral leishmaniasis (VL) is a chronic systemic disease caused by Leishmania infantum parasites, prevalent in the Americas. However, the toxicity of antileishmanial drugs, long treatment courses, and limited efficacy remain significant concerns that hinder the effective treatment of this disease. Recent studies have shown the potential of combining antileishmanial drugs with vaccine immunogens as an immunotherapeutic approach, to reduce parasitism and activate the host immune system.

Objetivo (s)

In this study, we developed an immunotherapy using a recombinant T-cell epitope-based chimeric protein called ChimT, known for its protective effect against Leishmania infantum, in combination with the adjuvant monophosphoryl lipid A (MPLA) and the antileishmanial drug amphotericin B (AmpB).

Material e Métodos

We tested this immunotherapy on BALB/c mice infected with L. infantum stationary promastigotes and compared the outcomes with other treatments and controls.

Resultados e Conclusão

The ChimT/MPLA/AmpB immunotherapy significantly reduced the parasite load in internal organs of the mice (P<0.05) and induced a Th1-type immune response, as evidenced by higher ratios of anti-ChimT and anti-parasite IgG2a:IgG1 antibodies, increased expression of IFN-γ mRNA and IFN-γ and IL-12 cytokines, and decreased levels of IL-4 and IL-10 cytokines (P<0.05). Moreover, the inclusion of vaccine and adjuvant in ChimT/MPLA/AmpB immunotherapy ameliorated the toxicity of AmpB to some extent. In addition, the ChimT vaccine alone stimulated murine macrophages in vitro to significantly kill internalized Leishmania parasites and produce Th1-type cytokines in culture supernatants. Our data suggest that the combination of ChimT/MPLA/AmpB could be a potential immunotherapeutic approach for L. infantum infection and warrants further investigation.

Palavras-chave

Visceral leishmaniasis; immunotherapy; chimera vaccine; T-cell response.

Agradecimentos

CNPq, FAPEMIG and CAPES.