Abstract
Development of a suitable vaccine against visceral leishmaniasis (VL), a fatal parasitic disease, is considered to be vital for maintaining the success of kala-azar control programs. The fact that Leishmania-infected individuals generate life-long immunity offers a viable proposition in this direction. Our prior studies demonstrated that T-helper1 (Th1) type of cellular response was generated by six potential recombinant proteins viz. elongation factor-2 (elF-2), enolase, aldolase, triose phosphate isomerase (TPI), protein disulfide isomerase (PDI) and p45, derived from a soluble antigenic fraction (89.9–97.1 kDa) of Leishmania (Leishmania) donovani promastigote, in treated Leishmania patients and golden hamsters and showed significant prophylactic potential against experimental VL. Moreover, since, it is well-known that our immune system, in general, triggers production of specific protective immunity in response to a small number of amino acids (peptide), this led to the identification of antigenic epitopes of the above-stated proteins utilizing immunoinformatics. Out of thirty-six, three peptides-P-10 (enolase), P-14, and P-15 (TPI) elicited common significant lymphoproliferative as well as Th1-biased cytokine responses both in golden hamsters and human subjects. Further, immunization with these peptides plus BCG offered 75% prophylactic efficacy with boosted cellular immune response in golden hamsters against Leishmania challenge which is indicative of their candidature as potential vaccine candidates.
Highlights
Visceral leishmaniasis (VL or kala-azar), caused by Leishmania (Leishmania) donovani and Leishmania (Leishmania) infantum is the most severe form of leishmaniasis wherein the immune system of the affected individuals is severely impaired making them susceptible to secondary infections [1]
Six recombinant Th1 stimulatory proteins namely aldolase, enolase, elongation factor-2 (elF-2), p45, protein disulfide isomerase (PDI), and triose phosphate isomerase (TPI) (Accession numbers: GQ220750.1, EU723850.1, EU929069.1, EU723851.1, EU723849.1, and EU867389.1, respectively), were expressed and purified using previously optimized protocols [18,19,20,21,22] and were used to compare the results obtained with the peptides identified in this study
Immuno Epitope Database (IEDB) and SYFPEITHI servers were used to predict immunogenic peptides from the full-length protein sequences of six potential Th1 stimulatory proteins (LdAld, LdEno, LdTPI, LdPDI, LdelF2, and Ldp45). Both servers yielded several peptides (>100) out of which six top scoring peptides were selected against the human leukocyte antigen (HLA) alleles which occurs most frequently in global population as well as against those recently reported to be involved in susceptibility to Leishmania infection in Indian population [27]
Summary
Visceral leishmaniasis (VL or kala-azar), caused by Leishmania (Leishmania) donovani and Leishmania (Leishmania) infantum is the most severe form of leishmaniasis wherein the immune system of the affected individuals is severely impaired making them susceptible to secondary infections [1]. The minimal immunogenic regions of a protein antigen, are the most precise vaccine components that guide the direction of immune responses, forms the basis of peptide-based synthetic vaccines [7]. A number of such vaccines have been evaluated against various parasitic diseases such as malaria, toxoplasmosis, and trypanosomiasis [10,11,12,13]. These vaccines offer several merits over conventional ones in terms of safety and regulatory issues and ease of production [7]
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