Abstract:
Visceral leishmaniasis (VL) is one of the most important parasitic diseases with approximately 350 million people at risk. Due
to the non availability of an ideal drug, development of a safe, effective, and affordable vaccine could be a solution for
control and prevention of this disease. In this study, a potential Th1 stimulatory protein- Triose phosphate isomerase (TPI), a
glycolytic enzyme, identified through proteomics from a fraction of Leishmania donovani soluble antigen ranging from
89.9–97.1 kDa, was assessed for its potential as a suitable vaccine candidate. The protein- L. donovani TPI (LdTPI) was cloned,
expressed and purified which exhibited the homology of 99% with L. infantum TPI. The rLdTPI was further evaluated for its
immunogenicity by lymphoproliferative response (LTT), nitric oxide (NO) production and estimation of cytokines in cured
Leishmania patients/hamster. It elicited strong LTT response in cured patients as well as NO production in cured hamsters
and stimulated remarkable Th1-type cellular responses including IFN-a˜ and IL-12 with extremely lower level of IL-10 in
Leishmania-infected cured/exposed patients PBMCs in vitro. Vaccination with LdTPI-DNA construct protected naive golden
hamsters from virulent L. donovani challenge unambiguously (,90%). The vaccinated hamsters demonstrated a surge in IFN-a˜ , TNF-a´ and IL-12 levels but extreme down-regulation of IL-10 and IL-4 along with profound delayed type
hypersensitivity and increased levels of Leishmania-specific IgG2 antibody. Thus, the results are suggestive of the protein
having the potential of a strong candidate vaccine.
