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Item A candidate vaccine for human visceral leishmaniasis based on a specific T cell epitope-containing chimeric protein protects mice against Leishmania infantum infection.(2020) Lage, Daniela Pagliara; Ribeiro, Patrícia Aparecida Fernandes; Dias, Daniel Silva; Mendonça, Débora Vasconcelos Costa; Ramos, Fernanda Fonseca; Carvalho, Lívia Mendes; Oliveira, Daysiane de; Steiner, Bethina Trevisol; Martins, Vivian Tamietti; Melo, Luísa Helena Perin de; Machado, Amanda Sanchez; Santos, Thaís Teodoro de Oliveira; Tavares, Grasiele de Sousa Vieira; Humbert, Maria Victoria; Coelho, Eduardo Antônio Ferraz; Christodoulides, MyronLeishmaniases 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.