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- Title
A candidate vaccine for human visceral leishmaniasis based on a specific T cell epitope-containing chimeric protein protects mice against Leishmania infantum infection.
- Authors
Lage, Daniela P.; Ribeiro, Patrícia A. F.; Dias, Daniel S.; Mendonça, Débora V. C.; Ramos, Fernanda F.; Carvalho, Lívia M.; de Oliveira, Daysiane; Steiner, Bethina T.; Martins, Vívian T.; Perin, Luísa; Machado, Amanda S.; Santos, Thaís T. O.; Tavares, Grasiele S. V.; Oliveira-da-Silva, João A.; Oliveira, Jamil S.; Roatt, Bruno M.; Machado-de-Ávila, Ricardo A.; Teixeira, Antônio L.; Humbert, Maria V.; Coelho, Eduardo A. F.
- 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.
- Subjects
VACCINES; VISCERAL leishmaniasis; PROHIBITIN; EPITOPES; T cells
- Publication
NPJ Vaccines, 2020, Vol 5, Issue 1, p1
- ISSN
2059-0105
- Publication type
Article
- DOI
10.1038/s41541-020-00224-0