Abstract
Visceral Leishmaniasis (VL), primarily caused by Leishmania donovani, presents a formidable public health challenge, with existing therapeutic options-such as pentamidine, amphotericin B, miltefosine, and paromomycin-being limited by adverse effects, high costs, restricted availability, and the emergence of drug-resistant strains. Despite the use of combination therapies, which have achieved an approximately 85% cure rate, the lack of a safe, effective, and durable vaccine remains a critical barrier to VL eradication. This study employed a comprehensive immuno-bioinformatics approach to design and analyse a multi-epitope vaccine candidate targeting essential immunogenic proteins in Leishmania spp: stress-induced proteins, Prohibitin (PHB), and GP63. These proteins play crucial roles in parasite survival, virulence, and host immune modulation. Our computational analysis identified epitopes from these proteins that were predicted to elicit strong humoral and cellular immune responses while being non-allergenic. The designed vaccine construct demonstrates substantial immunogenic potential, highlighting its promise as a candidate for further preclinical and clinical evaluation in pursuing an effective VL vaccine. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40203-025-00433-2.