Research Projects

Kala-azar or visceral leishmaniasis (VL) is a substantial public health problem and is globally prevalent in more than 75 countries. The sporadic cases of VL in non-endemic parts of India and the recurrence of disease in endemic blocks become a barrier to the elimination program. The effective management of VL necessitates the formulation of a prophylactic vaccine is a high priority of the research. The classical vaccines developed with whole parasites and their proteins were associated with several drawbacks and proved to be unsuccessful in developing a licensed vaccine for human VL. The reasons are uncertain knowledge of immunopathogenesis, antigen variation, gene polymorphism in the parasite, and differential antigen presentation to B and T cells. In the recent past, specific peptide (epitope)-based vaccine design has become a promising approach due to its advantages over the conventional vaccines, owed to be their (synthetic) low cost and ease to scale up, stability, less antigen complexity, and absence of potential damaging fractions. Though peptide vaccines are poor immunogens, in combination with potential adjuvants, they could generate long-lasting specific immune responses. However, the identification of such a reliable vaccine candidate is a challenging task where the unique presence of Leishmania peptides or epitopes could be considerable alternatives for potential vaccines. Fascinatingly, we found a unique peptide stretch in the Leishmania donovani 3-mercaptopyruvate sulfurtransferase (Ld3MST). Though 3-MST is present across the species from bacteria to humans, its functions are well explored only in E. coli, mice, and humans but remained scarce in Leishmania. Typically, Ld3MST facilitates sulfide for de novo biosynthesis of cysteine by acting upon 3-mercaptopyruvate. Hence, it is involved in thiol metabolism and redox homeostasis, which are crucial for the parasite's survival in the hostile environment (oxidative stress) of the host. The sequence of 3-MST protein shows an elongated ~70 amino acids region at the C-terminus in Leishmania but is absent in humans and mice. We anticipate that this unique region of Ld3MST is likely to be a potential antigen during actual infection and could offer long-lasting cell-mediated immunity while host protection. In this study, we proposed to conduct in silico prediction of immunogenic epitopes from this unique region and validation of their binding affinity with major histocompatibility complex (MHC) and toll-like receptors (TLR), then, in vitro validation of their immunogenicity in human peripheral blood mononuclear cells (PBMCs) and in vivo evaluation of their immunoprophylactic activity against L. donovani challenge in animal model would provide further insights for vaccine development. The whole peptide stretch would also act as a potential antigen to react with patient sera and provide insight for the development of diagnostic tools.