Evaluation of <i>Leishmania</i> homolog of activated C kinase (LACK) of <i>Leishmania donovani</i> in comparison to glycoprotein 63 as a vaccine candidate against visceral leishmaniasis

Leishmaniasis, caused by <i>Leishmania</i> protozoa transmitted via sand fly bites, affects over 12 million people annually, manifesting as self-limiting cutaneous lesions or fatal visceral leishmaniasis (VL). The disease's immune response involves a Th1/Th2 paradigm, with Th1 promoting resistance and Th2 linked to susceptibility. Despite no available human vaccine, the <i>Leishmania</i> homolog of activated C kinase (LACK) protein has shown promise as a candidate due to its conservation across species. In this study, we purified the native 34 kDa LACK protein from <i>Leishmania donovani</i> promastigotes and compared its efficacy with that of gp63 in cationic DSPC liposomes. While gp63 exhibited protective efficacy, LACK failed to protect BALB/c mice. Recombinant LACK, which was cloned, expressed, and purified, also did not confer protection. Immunological assays revealed a Th2-biased immune response characterized by a high IgG1/IgG2a ratio, elevated Th2 cytokines, and an unaltered delayed-type hypersensitivity (DTH) response, highlighting its limited potential.IMPORTANCEThis study underscores the limitations of LACK as a standalone vaccine candidate against VL. Both native and recombinant LACK forms, despite liposomal encapsulation, elicited a Th2-dominated immune response, inadequate for protection. These findings suggest that LACK's intrinsic immunogenic properties may not support the robust Th1 response crucial for combating <i>Leishmania donovani</i> infections. Future research should prioritize alternative antigens or combination formulations to promote Th1-driven immunity. This work contributes to the growing body of knowledge guiding vaccine development for VL, emphasizing the need for immunogens that effectively target protective immune pathways.