A candidate vaccine for human visceral leishmaniasis based on a specific T cell epitope-containing chimeric protein protects mice against Leishmania infantum infection

Pagliara Lage, Daniela, Ribeiro, Patricia, Dias, Daniel, Mendonca, Debora V.C., Fonseca Ramos, Fernanda, Carvalho, Livia M., de Oliveira, Daysiane, Steiner, Bethina T., Martins, Vivian T., Perin, Luisa, Sanchez Machado, Amanda, Santos, Thais T.O., Tavares, Grasiele S.V., Oliviera-da-Silva, Jaoa A., Oliveira, Jamil S., Roatt, Bruno M., Machado-de-Avila, Ricardo A., Teixeira, Antonio L., Humbert, Maria, Ferraz Coelho, E. A. and Christodoulides, Myron (2020) A candidate vaccine for human visceral leishmaniasis based on a specific T cell epitope-containing chimeric protein protects mice against Leishmania infantum infection. NPJ Vaccines, 5 (1), [75]. (doi:10.1038/s41541-020-00224-0).

Abstract

Leishmaniases are neglected diseases caused by infection with Leishmania parasites and there are currently no prophylactic vaccines. In this study, we designed in silico a synthetic recombinant vaccine against visceral leishmaniasis (VL) called ChimeraT, which contains specific T-cell epitopes from Leishmania Prohibitin, Eukaryotic Initiation Factor 5a and the hypothetical LiHyp1 and LiHyp2 proteins. Subcutaneous delivery of ChimeraT plus saponin stimulated a Th1 cell-mediated immune response and protected mice against L. infantum infection, significantly reducing the parasite load in distinct organs. ChimeraT/saponin vaccine stimulated significantly higher levels of IFN-γ, IL-12, and GM-CSF cytokines by both murine CD4 ⁺ and CD8 ⁺ T cells, with correspondingly low levels of IL-4 and IL-10. Induced antibodies were predominantly IgG2a isotype and homologous antigen-stimulated spleen cells produced significant nitrite as a proxy for nitric oxide. ChimeraT also induced lymphoproliferative responses in peripheral blood mononuclear cells from VL patients after treatment and healthy subjects, as well as higher IFN-γ and lower IL-10 secretion into cell supernatants. Thus, ChimeraT associated with a Th1 adjuvant could be considered as a potential vaccine candidate to protect against human disease.

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Contributors

Author: Maria Humbert

Author: Myron Christodoulides

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