A new chimeric protein composed by T-cell epitopes from peroxidoxin and pyridoxal kinase proteins is protective against visceral leishmaniasis

Lage D.P.; Vale D.L.; Silva M.G.P.; Martins V.T.; Gonçalves A.A.M.; Silva K.A.; Moreira G.J.L.; Olegário R.D.; Rizzatti F.C.; Freitas C.S.; Pimenta B.L.; Falcão K.O.M.; Dias S.S.G.; Oliveira-da-Silva J.A.; Câmara R.S.B.; Pereira I.A.G.; Chávez-Fumagalli M.A.; Roatt B.M.; Machado-de-Ávila R.A.; Galdino A.S.; Coelho E.A.F. · Cellular Immunology (2025) · DOI: 10.1016/j.cellimm.2025.104949

Resumen

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.

Instituciones: Universidad Católica de Santa María