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bioRxiv · 10.1101/2025.06.25.661467

Evaluation of Leishmania Homologue of Activated C Kinase (LACK) of Leishmania donovani in comparison to glycoprotein 63 as vaccine candidate against visceral leishmaniasis

Didwania, N.·Bhowmick, S.·Sabur, A.·Bhattacharya, A.·Ali, N.
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Abstract

Leishmaniasis, caused by Leishmania protozoa transmitted via sand fly bites, affects over 12 million people annually, manifesting as self-limiting cutaneous lesions or fatal visceral leishmaniasis (VL). The diseases immune response involves a Th1/Th2 paradigm, with Th1 promoting resistance and Th2 linked to susceptibility. Despite no available human vaccine, the Leishmania homologue of activated C kinase (LACK) protein has shown promise as a candidate due to its conservation across species. In this study, we purified native 34-kDa LACK protein from Leishmania donovani promastigotes and compared its efficacy with 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 LACKs intrinsic immunogenic properties may not support the robust Th1 response crucial for combating Leishmania donovani 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.

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Didwania, N., Bhowmick, S., Sabur, A., Bhattacharya, A., Ali, N.. 2025-06-27. Evaluation of Leishmania Homologue of Activated C Kinase (LACK) of Leishmania donovani in comparison to glycoprotein 63 as vaccine candidate against visceral leishmaniasis. https://doi.org/10.1101/2025.06.25.661467

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