Tomatine Augments T Cell-Mediated Protective Immunity Induced by First-Generation Leishmania Antigen Against Visceral Leishmaniasis

First-generation vaccine candidates against leishmaniasis, based on chemically or physically inactivated whole parasite, have attracted considerable attention owing to their feasibility, scalability of production, and comparatively low manufacturing costs. Vaccine formulations typically require immunostimulatory compounds to elicit robust cell-mediated immunity. Traditionally, adjuvants have been incorporated into vaccine formulation to augment their immunogenic potential. Recent advances over the past decade have yielded novel adjuvant system capable of stimulating both antibody-mediated and cell-mediated immune pathways. Recent advances in adjuvant development have facilitated the design of several promising vaccine candidates against leishmaniasis. Therefore, in the present study, we tested tomatine (identified as a steroidal glycoalkaloid, a saponin subgroup), for its ability to induce cell-mediated immunity that confer protection against leishmaniasis. Tomatine, a glycoalkaloid based adjuvant, possesses the ability to elicit cytotoxic T-lymphocyte responses. It shows remarkable potential as an effective adjuvant candidate for vaccine applications targeting infectious pathogens. Our results demonstrated that tomatine combined with the first-generation antigen induced durable central (CD44highCD62Lhigh) and effector (CD44highCD62Llow) memory CD4⁺ and CD8⁺ T-cell responses in both pre-challenge and post-challenge mice, indicating the development of long-lasting protective cellular immunity. Significant protective immunity was further demonstrated in the vaccinated animals, as evidenced by remarkably declined parasite burden, increased levels of T cells (CD4+, CD8+), IFN-γ, GM-CSF, effector molecules i.e. reactive oxygen species and nitric oxide and heightened NF-kB and iNOS gene expression. Collectively, these findings highlight tomatine as an effective immunomodulatory adjuvant capable of inducing cell-mediated protective immunity against leishmaniasis.