Leishmania donovani triose phosphate isomerase: a potential vaccine target against visceral leishmaniasis

Kushawaha, Pramod K. ; Gupta, Reema ; Tripathi, Chandra Dev Pati ; Khare, Prashant ; Jaiswal, Anil Kumar ; Sundar, Shyam ; Dube, Anuradha (2012) Leishmania donovani triose phosphate isomerase: a potential vaccine target against visceral leishmaniasis PLoS One, 7 (9). Article ID e45766, 12 pages. ISSN 1932-6203

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Official URL: http://journals.plos.org/plosone/article?id=10.137...

Related URL: http://dx.doi.org/10.1371/journal.pone.0045766


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-ã 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-ã, TNF-á 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.

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