Leishmania donovani Triose Phosphate Isomerase: A Potential Vaccine Target against Visceral Leishmaniasis

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-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.

Vaccination with cyclin-dependent kinase tick antigen confers protection against Ixodes infestation

“…Previously, the selection of antigens for developing vaccines has predominantly focused on extracellular protein targets, on the premise that intracellular proteins are not accessible to antibodies. However, there is ample evidence suggesting that intracellular proteins might be useful targets for vaccination against ticks and other parasites (Parizi et al, 2011;Balaban et al, 1995;Kushawaha et al, 2012). Taken together, these results indicate that CDKs are suitable targets for designing vaccines against for Ixodes tick species.…”

Visceral Leishmaniasis: Advancements in Vaccine Development via Classical and Molecular Approaches

“…Kushawaha et al (48, 50, 51) studied the immunogenicity of LelF-2, TPI, and PDI of L. donovani in PBMCs of cured Leishmania -infected patients and hamsters where they found Thl-type cytokine profile (production of IFN-γ, IL-12, and TNF-α but not IL-4 or IL-10) with a remarkable increase in IgG2 and considerable protection. Gupta et al (49, 53) reported p45, enolase, and aldolase as a potential vaccine candidate with considerable prophylactic efficacy to the tune of 85–90% with an increased mRNA expression of iNOS, IFN-γ, TNF-α, and IL-12 and decrease in TGF-β and IL-4.…”

Comparison of PCR methods for detection of Leishmania siamensis infection

“…Accordingly, PCR methods have been widely used to detect Leishmania infection in clinical specimens with a high sensitivity and specificity [13]. Several PCR approaches have been published based on different target genes, i.e., the cysteine protease B (cpb) [14], the cytochrome b (cyt b) [15], the internal transcribed spacer 1 (ITS1) region of the small subunit ribosomal RNA (SSU-rRNA) gene [16], the glucose-6-phosphate dehydrogenase (G6PD) [17], the heat shock protein 70 (hsp70) [18], the spliced leader mini-exon [19], the SSU-rRNA gene [20] and the triose-phosphate isomerase (tim) genes [21]. Of these, the ITS1 region of the SSU-rRNA gene has been one of the common genetic markers used to detect Leishmania species in the Old World [13,16,[22][23][24].…”