In silico designing of a novel polyvalent multi-subunit peptide vaccine leveraging cross- immunity against human visceral & cutaneous leishmaniasis: An Immunoinformatics-based approach

Abstract

Abstract Leishmaniasis necessitates grave medical concern due to emergence of drug resistant strains & adverse side effects of the drugs. Already set foot in the endemic disease to tropical & subtropical countries in the world. Presently no promising & apposite vaccination strategy exists as curative therapy. In this study, we have designed for the first time a multi-subunit peptide vaccine that may confer cross-immunity against both visceral leishmaniasis (VL) & cutaneous leishmaniasis (CL) in humans. It is based on twelve experimentally validated leishmania-specific antigenic proteins that stem from multiple pathogenic species of Leishmania. Immuno-dominant B/T-cell epitopes were identified, amalgamated with proper linker & appropriate adjuvant (IL-12) to enhance the immunogenicity. Further, various physicochemical parameters, allergenicity, antigenicity and toxicity of the vaccine were also predicted to ensure the safety of the final vaccine construct. Homology modeling was performed to predict the structure of the proposed vaccine peptide & interactions with the TLR receptors were studied by molecular docking approach. Stability of the vaccine-TLR complex was also studied by implementing molecular dynamics simulation. Again mRNA structure prediction, codon optimization and in silico cloning of the corresponding gene sequence were carried out in order to anticipate the amenability of the gene construct to get expressed under in vitro system. Finally, computational immune simulation findings reveal promising cellular & humoral immune responses. Thereupon our engineered chimeric peptide appears to be a potential vaccine candidate against VL & CL.