Leishmania donovani Triose Phosphate Isomerase: A Potential Vaccine Target against Visceral Leishmaniasis
IR@CDRI: CSIR-Central Drug Research Institute, Lucknow
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Creator |
Kushawaha, P K
Gupta, Reema Tripathi, C D P Khare, Prashant Jaiswal, A K Sundar, Shyam Dube, Anuradha |
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Date |
2013-06-21T06:20:02Z
2013-06-21T06:20:02Z 2012 |
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Identifier |
PLoS ONE 7(9): e45766
http://hdl.handle.net/123456789/1077 |
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Description |
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.
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Format |
635076 bytes
application/pdf |
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Language |
en
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Relation |
8321
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Subject |
LdTPI
Visceral leishmaniasis Peripheral blood mononuclear cells Inducible NO synthase L. donovani Triose phosphate isomerase |
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Title |
Leishmania donovani Triose Phosphate Isomerase: A Potential Vaccine Target against Visceral Leishmaniasis
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Type |
Article
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