Evaluation of Leishmania homolog of activated C kinase (LACK) of Leishmania donovani in comparison to glycoprotein 63 as a vaccine candidate against visceral leishmaniasis
Year: 2025
Type: article
Abstract: 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 disease’s 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. Importance This 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 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.
Source: Microbiology Spectrum
Authors: Nicky Didwania, Sudipta Bhowmick, Abdus Sabur, Anirban Bhattacharya, Nahid Ali
Language: English
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,500
OpenAlex ID: W4413311490