Elucidation of conserved multi-epitope vaccine against <i>Leishmania donovani</i> using reverse vaccinology

Visceral leishmaniasis (VL) is a tropical disease that causes severe public health problems in humans when untreated. As no licensed vaccine exists against VL, we aimed to formulate a potential MHC-restricted chimeric vaccine construct against this dreadful parasitic disease. Amastin-like protein derived from <i>L. donovani</i> is considered to be stable, immunogenic and non-allergic. A comprehensive established framework was used to explore the set of immunogenic epitopes with estimated population coverage of 96.08% worldwide. The rigorous assessment revealed 6 promiscuous T-epitopes which can plausibly be presented by more than 66 diverse HLA alleles. Further docking and simulation study of peptide receptor complexes identified a strong and stable binding interaction with better structural compactness. The predicted epitopes were combined with appropriate linkers and adjuvant molecules and their translation efficiency was evaluated in pET28+(a), an bacterial expression vector using in-silico cloning. Molecular docking followed by MD simulation study revealed a stable interaction between chimeric vaccine construct with TLRs. Immune simulation of the chimeric vaccine constructs showed an elevated Th1 immune response against both B and T epitopes. With this, the detailed computational analysis suggested that the chimeric vaccine construct can evoke a robust immune response against <i>Leishmania donovani</i> infection. Future studies are required to validate the role of amastin as a promising vaccine target. Communicated by Ramaswamy H. Sarma