Therapeutic evaluation of a first-generation L. amazonensis antigen vaccine with TLR-3 ligand adjuvant.

Leishmaniasis is an expanding parasitic zoonosis in South America and is considered one of the neglected diseases by the WHO because it primarily affects low-income populations with limited access to healthcare services. Currently, there is no vaccine available for the prevention of human leishmaniasis, and existing treatments, such as Glucantime®, although effective, are limited by prolonged administration, significant toxicity, and severe adverse effects. Therefore, the development of innovative immunotherapeutic alternatives based on first-generation vaccines is urgently needed. In this study, we evaluated the therapeutic effect of a vaccine formulated with total antigens of Leishmania amazonensis (TLA) and the TLR3 agonist Poly (I:C) as an adjuvant. Our previous studies demonstrated that this vaccine formulation, when administered prophylactically, induces a protective Th1 immune response. Female BALB/c mice were infected with 1 × 10⁴ L. amazonensis promastigotes and treated with the TLA + Poly (I:C) formulation. The TLA + Poly (I:C) vaccine failed to control disease progression, as evidenced by footpad swelling of 1.238 ± 0.174 mm, lesion weight of 0.465 ± 0.055 g, a parasite burden index of 8.667 ± 0.333, and total IgG levels of OD 1.165 ± 0.034 at the end of the treatment period. In contrast, Poly (I:C)-treated mice exhibited significantly lower footpad swelling (0.739 ± 0.111 vs. 1.185 ± 0.168 mm, p < 0.01), lesion weight (0.167 ± 0.041 vs. 0.373 ± 0.065 g, p < 0.001), parasite burden index (7.000 ± 0.000 vs. 8.333 ± 0.333, p < 0.05), and total IgG levels (OD 0.670 ± 0.089 vs. 0.965 ± 0.083, p < 0.05) compared with PBS-treated mice. These results highlight the potential of TLR ligands as therapeutic strategies for leishmaniasis. Their ability to modulate both innate and adaptive immune responses makes them promising candidates for the development of novel immunotherapeutic approaches. Future research focusing on specific ligand-antigen combinations is essential to optimize their therapeutic efficacy.