A Leishmania hypothetical protein-containing liposome-based formulation is highly immunogenic and induces protection against visceral leishmaniasis

Cytokine. 2018 Nov:111:131-139. doi: 10.1016/j.cyto.2018.08.019. Epub 2018 Aug 22.

Abstract

Leishmania proteins have been evaluated as vaccine candidates against leishmaniasis; however, most antigens present low immunogenicity and need to be added with immune adjuvants. A low number of licensed adjuvants exist on the market today; therefore, research conducted to produce new products is desirable. The present study sought to evaluate the immunogenicity and protective efficacy of a recombinant Leishmania hypothetical protein, namely LiHyR, administered with saponin or liposomes in BALB/c mice. Immunological and parasitological parameters were evaluated, and results showed significant protection against Leishmania infantum infection produced by both compositions in the immunized animals; however, this was not identified when the antigen was used alone. In addition, the liposomal formulation was more effective in inducing a polarized Th1 response in the vaccinated animals, which was maintained after challenge and reflected by lower parasitism found in all evaluated organs when the limiting dilution technique and RT-PCR assay were employed. The protected animals showed higher levels of protein and parasite-specific IFN-γ IL-2, IL-12, GM-CSF, and TNF-α, which were evaluated by capture ELISA and flow cytometry, in addition to a higher production of anti-protein and anti-parasite IgG2a antibodies, both before and after challenge. The Lip/rLiHyR combination induced higher IFN-γ production through both CD4+ and CD8+ T cell subtypes. Results indicate the possibility of using the LiHyR, containing a liposomal formulation, as a vaccine candidate against visceral leishmaniasis.

Keywords: Adjuvants; Hypothetical proteins; Liposomes; Saponin; Vaccine; Visceral leishmaniasis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / pathology
  • CD8-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / pathology
  • Cytokines / immunology*
  • Immunogenicity, Vaccine*
  • Leishmania infantum / immunology*
  • Leishmaniasis Vaccines / immunology
  • Leishmaniasis Vaccines / pharmacology*
  • Leishmaniasis, Visceral / immunology
  • Leishmaniasis, Visceral / pathology
  • Leishmaniasis, Visceral / prevention & control*
  • Liposomes
  • Mice
  • Mice, Inbred BALB C
  • Protozoan Proteins / immunology
  • Protozoan Proteins / pharmacology*

Substances

  • Cytokines
  • Leishmaniasis Vaccines
  • Liposomes
  • Protozoan Proteins