Evaluation of Transgenic Iranian Lizard Leishmania Encoding Human IL-۱۲ as a Candidate Vaccine Against Experimental Cutaneous Leishmaniasis in Susceptible BALB/c Mice

Introduction: Leishmaniasis is a neglected tropical disease that causes significant morbidity worldwide, particularly in developing countries. Despite ongoing efforts, there is no widely approved human vaccine against this disease. Live, non-pathogenic organisms such as Leishmania tarentolae have emerged as promising candidates for vaccine development due to their safety profile and ability to present antigens in a native context. This study aimed to evaluate transgenic Iranian Lizard Leishmania (I.L.L.) encoding human IL-۱۲ (hIL-۱۲) as a candidate vaccine against experimental cutaneous leishmaniasis in susceptible BALB/c mice. Methods: BALB/c mice were divided into six groups and immunized subcutaneously with either transgenic L. tarentolae-hIL-۱۲ (G۱ and G۲), wild-type L. tarentolae (G۳ and G۴), or RPMI-۱۶۴۰ medium (G۵ and G۶). Three weeks post-immunization, animals received a booster injection. Two weeks after the booster, challenged groups (G۱, G۳, and G۵) were infected with Leishmania major promastigotes. Lesion progression was measured weekly for ۱۱ weeks. IgG۲a responses were assessed using ELISA, while cytokine responses (IFN-γ, IL-۱۷, IL-۱۰, TNF-α) were quantified after stimulation with soluble L. major antigen (SLA). Parasite burden in spleens was evaluated by real-time PCR. Results: Mice vaccinated with transgenic I.L.L.-hIL-۱۲ developed significantly stronger cellular and humoral immune responses than the control groups. Elevated IFN-γ, IL-۱۷ and IgG۲a levels indicated a predominantly Th۱-biased immune response, while increased IL-۱۰ production suggested a concomitant regulatory response. Vaccinated mice also exhibited smaller lesion sizes and lower splenic parasite burdens than the control groups, indicating partial protection against L. major infection. Conclusion: The transgenic L. tarentolae-hIL-۱۲ strain effectively induced protective immunity in susceptible BALB/c mice, supporting its potential as a novel and safe live vaccine platform for cutaneous leishmaniasis due to L. major.

کلیدواژه ها:

Leishmania tarentolae ، Leishmania major ، Interleukin-۱۲ ، Vaccines ، Parasite burden