Enhancing memory T cell responses through Soluble Leishmania antigen and natural adjuvants against Leishmania donovani in murine model.

Leishmaniasis, caused by Leishmania spp., is a major public health concern in tropical and subtropical regions and is classified as a neglected tropical disease (NTD). Visceral leishmaniasis (VL), the most severe form, affects the reticuloendothelial system and is often fatal if untreated. Current treatment relies on a limited number of chemotherapeutic agents, and no licensed vaccine is available to prevent infection. This highlights the urgent need for a prophylactic vaccine to protect against the infection and its potentially fatal consequences. Therefore, in the present study, we evaluated the efficacy of quercetin and tomatine in combination with first-generation antigen of Leishmania donovani in a murine model. Immunological and parasitological parameters were carried out to determine the protective efficacy of the vaccine formulations, both pre-challenge and 12 weeks post-challenge infection. Our results demonstrated that immunized mice exhibited enhanced CD4+ and CD8+ T-cell responses with Th1 cytokine profile, accompanied by the generation of central and effector memory T cells in splenocytes. Furthermore, vaccination significantly reduced hepatic parasite load and was associated with increased production of reactive oxygen species and nitric oxide, as well as upregulated expression of iNOS and NF-κB. These findings suggest that quercetin and tomatine-based vaccine formulations can effectively stimulate protective cell-mediated immunity and parasite clearance. The results provide strong evidence supporting their potential as candidate vaccines for VL, contributing to ongoing efforts in leishmaniasis vaccine development.