Recombinant vaccine plus anti-parasitic agent in an immunotherapeutic schedules induce partial regression of tegumentary leishmaniasis in a murine model

Freitas C.S.; Lage D.P.; Pimenta B.L.; Falcão K.O.M.; Moreira G.J.L.; Pereira I.A.G.; Câmara R.S.B.; Simão L.P.; Silva A.L.; Oliveira-da-Silva J.A.; Abrão D.M.; Galdino A.S.; Chávez-Fumagalli M.A.; Roatt B.M.; Christodoulides M.; Coelho E.A.F. · Vaccine (2026) · DOI: 10.1016/j.vaccine.2026.128990

Resumen

Tegumentary leishmaniasis (TL) is a neglected tropical disease characterized by limited therapeutic options, drug-associated toxicity, and the absence of immunotherapeutic interventions. In this study, we evaluated an immunochemotherapeutic strategy combining the multi-epitope recombinant protein ChimT, monophosphoryl lipid A (MPLA), and ivermectin (IVE) for the treatment of Leishmania amazonensis infection in BALB/c mice. Infected animals were treated with ChimT, MPLA, and/or IVE; and parasitological, immunological, and biochemical evaluations were performed one and 30 days after therapy. The ChimT/MPLA/IVE combination induced the most robust therapeutic response in comparison to all evaluated groups. These animals exhibited enhanced Th1-type immunity, characterized by significantly higher levels of IFN-γ, IL-12, TNF-α, nitrite, and increased anti-protein and anti-parasite IgG2a:IgG1 ratios, while significantly higher levels IL-4 and IL-10 were found in saline group mice. Both CD4+ and CD8+ T-cell subtypes contributed to IFN-γ production in ChimT/MPLA/IVE-treated mice, which was further supported by increased IFN-γ mRNA expression and significantly higher frequencies of both IFN-γ- and TNF-α-producing T-cells, as compared to saline group. ChimT/MPLA/IVE induced strong delayed-type hypersensitivity response and maintained normal hematological parameters. Importantly, the combination promoted substantial and sustained reductions in parasite burden, with significantly lowers of parasite load in the evaluated organs and tissues, as compared to data of saline group. No significant toxicity was also found in all animals, when hepatic and renal damage markers were evaluated. Collectively, the findings suggest that ChimT/MPLA/IVE elicits Th1-type immune responses and partial parasitism control in treated animals, indicating the feasibility to test such combination in future studies for the treatment against TL.

Instituciones: Universidad Católica de Santa María