Abstract
Our prior studies demonstrated that cellular response of T helper 1 (Th1) type was generated by a soluble antigenic fraction (ranging from 89.9 to 97.1 kDa) of Leishmania donovani promastigote, in treated Leishmania patients as well as hamsters and showed significant prophylactic potential against experimental visceral leishmaniasis (VL). Eighteen Th1 stimulatory proteins were identified through proteomic analysis of this subfraction, out of which 15 were developed as recombinant proteins. In the present work, we have evaluated these 15 recombinant proteins simultaneously for their comparative cellular responses in treated Leishmania patients and hamsters. Six proteins viz. elongation factor-2, enolase, aldolase, triose phosphate isomerase, protein disulfide isomerase, and p45 emerged as most immunogenic as they produced a significant lymphoproliferative response, nitric oxide generation and Th1 cytokine response in PBMCs and lymphocytes of treated Leishmania patients and hamsters respectively. The results suggested that these proteins may be exploited for developing a successful poly-protein and/or poly-epitope vaccine against VL.
Highlights
Visceral leishmaniasis (VL), a life-threatening systemic disease referred as black sickness or kala-azar, is caused by Leishmania (L.) donovani and L. infantum and is transmitted to the human host via the bite of infected female dipteran vector, sandfly
Fifteen recombinant T helper 1 (Th1) stimulatory proteins utilized in this study namely elongation factor-2, p45, aldolase (Aldo), enolase (Eno), triosephosphate isomerase (TPI), protein disulfide isomerase (PDI), cofactor-independent phosphoglycerate mutase, adenosyl homocysteinase (ADHT), calreticulin (Cal), heat shock proteins (Hsp) – Hsp70 and Hsp83, trypanothione reductase (TPR), NAD-dependent deacetylase SIR2 homolog (NAD) and two hypothetical proteins (Hypo 1 and 2) have been successfully cloned, expressed and purified
Ten recombinant proteins viz. rLdEno, rLdPDI, rLdTPI, rLdelF-2, rLdp45, rLdAldo, rLdADHT, rHsp83 and the two hypothetical proteins- rLdHypo1 and rLdHypo2 showed significantly higher stimulation in lymphocytes isolated from treated hamsters than Soluble L. donovani (SLD)
Summary
Visceral leishmaniasis (VL), a life-threatening systemic disease referred as black sickness or kala-azar, is caused by Leishmania (L.) donovani and L. infantum (chagasi) and is transmitted to the human host via the bite of infected female dipteran vector, sandfly. This disease is widespread in the Indian subcontinent, East Africa, Mediterranean basin, Central and South America. Considering the existence of 80–90% of subclinical or asymptomatic Leishmania cases (endemic healthy contacts) as well as post kala-azar dermal leishmanoid (PKDL) cases, a safe and effective vaccine will be critical if the success of recent VL control efforts in Indian subcontinent is to be sustained (Engwerda and Matlashewski, 2015)
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