A candidate vaccine for human visceral leishmaniasis based on a specific T cell epitope-containing chimeric protein protects mice against Leishmania infantum infection
| Autor: | Jamil S. Oliveira, Myron Christodoulides, Ricardo Andrez Machado-de-Ávila, Patrícia A.F. Ribeiro, Lívia M. Carvalho, Bethina T. Steiner, Vívian T. Martins, Grasiele S.V. Tavares, Daysiane de Oliveira, Luísa Perin, Thaís T.O. Santos, Fernanda F. Ramos, Eduardo A.F. Coelho, Daniel Dias, Débora V.C. Mendonça, Bruno Mendes Roatt, Daniela P. Lage, Antônio Lúcio Teixeira, Amanda S. Machado, Maria Victoria Humbert, João A. Oliveira-da-Silva |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
lcsh:Immunologic diseases. Allergy medicine.medical_treatment T cell Immunology Peripheral blood mononuclear cell lcsh:RC254-282 Epitope 03 medical and health sciences 0302 clinical medicine Immune system parasitic diseases medicine Pharmacology (medical) Pharmacology biology biology.organism_classification medicine.disease lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens Virology 030104 developmental biology Infectious Diseases Visceral leishmaniasis medicine.anatomical_structure biology.protein Leishmania infantum Antibody lcsh:RC581-607 Adjuvant 030215 immunology |
| Zdroj: | npj Vaccines, Vol 5, Iss 1, Pp 1-13 (2020) |
| ISSN: | 2059-0105 |
| DOI: | 10.1038/s41541-020-00224-0 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|