Cellular immunology · 2025
A new chimeric protein composed by T-cell epitopes from peroxidoxin and pyridoxal kinase proteins is protective against visceral leishmaniasis.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Lage Daniela P, Vale Danniele L, Silva Marcela G P, Martins Vívian T, Gonçalves Ana A M, Silva Kamila A, Moreira Gabriel J L, Olegário Rafaela D, Rizzatti Flávia C, Freitas Camila S, Pimenta Breno L, Falcão Karolina O M, Dias Saulo S G, Oliveira-da-Silva João A, Câmara Raquel S B, Pereira Isabela A G, Chávez-Fumagalli Miguel A, Roatt Bruno M, Machado-de-Ávila Ricardo A, Galdino Alexsandro S, Coelho Eduardo A F
Аннотация
Visceral leishmaniasis (VL) is a neglected tropical disease caused by intracellular protozoan parasites, and which present high incidence in populations in the world. The diagnosis is difficult to be performed, and treatment is toxic and/or presents high cost. In this context, prophylactic vaccination could help as an effective control measure against the disease. In this study, a new chimeric protein (LAV) was constructed with immunogenic T-cell epitopes from two immunogenic Leishmania proteins, and it was evaluated to protects BALB/c mice against Leishmania infantum infection. For this, animals were vaccinated with rLAV associated with micelles (Mic) or monophosphoryl lipid A (MPLA) as adjuvants; while the others received saline, rLAV, Mic or MPLA as controls. Results showed that the rLAV/Mic and rLAV/MPLA combinations induced higher cell proliferation indexes in stimulated cell cultures after infection, as well as the development of a polarized Th1-type cellular and humoral response before and after infection, which was based on the production of IFN-γ, IL-12, TNF-α, nitrite, and IgG2a isotype antibodies. In addition, both CD4+ and CD8+ T-cell subtypes were important for the IFN- secretion in both groups, as compared to the others. Control groups mice produced significantly higher levels of IL-4, IL-10 and anti-parasite IgG1 antibodies, suggesting the occurrence of a Th2-type immune profile in these unprotected animals. The parasite load was found to be significantly lower in mice vaccinated with rLAV/MPLA or rLAV/Mic, as compared to the others, by using a limiting dilution assay and qPCR. In conclusion, data suggest that rLAV plus adjuvant could be considered as a vaccine candidate in future studies to protect against VL.