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 vaccination could represent a control measure against disease. In this study, the protective efficacy of Leishmania LiHyC protein was evaluated in a murine model against Leishmania 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 expression 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 associated with adjuvants could be considered for future studies as a vaccine candidate against VL.

A Recombinant Chimeric Protein-Based Vaccine Containing T-Cell Epitopes from Amastigote Proteins and Combined with Distinct Adjuvants, Induces Immunogenicity and Protection against Leishmania infantum Infection

“…Since amastigotes display fewer antigens than promastigotes, vaccines that direct the host immune response towards specific amastigote antigens could protect against infection [ 29 ]. In our current study, the LiHyp1 [ 37 ], LiHyV [ 38 ], LiHyC [ 39 ] and LiHyG [ 30 ] proteins that we selected are all found in the L. infantum amastigote stage and a chimeric vaccine was developed using the main T-cell epitopes from each protein. The rationale for this approach is supported by previous studies using single, recombinant parasite proteins and chimeric proteins containing antigens expressed in the promastigote stage of the parasites [ 22 , 40 ].…”