Designing of peptide based multi-epitope vaccine construct against gallbladder cancer using immunoinformatics and computational approaches

Abstract Gallbladder cancer (GBC) is an aggressive and difficult to treat biliary tract carcinoma characterised by late presentation, poor prognosis, and a survival rate of <1 year. GBC is difficult to treat and the current treatments have yielded dismal outcomes. The aim of this study was to design a multi-epitope vaccine candidate against GBC using reverse vaccinology and immunoinformatics tools. Epitopes from three antigenic proteins (NT5E, ANPEP and MME) were used for designing the epitope vaccine. CTL, HTL and B-cell epitopes were predicted and screened on the basis of immunogenicity, antigenicity, allergenicity, toxicity and IFN-γ inducing properties. The selected epitopes were connected using linkers and suitable adjuvant for designing final vaccine construct. The physicochemical properties were analysed followed by 2D and 3D structure generation, refinement and validation. The binding affinity of vaccine construct with immune receptors (TLR2, 3 and 4) was assessed through molecular docking. The stability of the docked vaccine-receptor complexes were evaluated using 100ns MD simulations. The epitope vaccine showed an adequate antibody and cell mediated immune responses through in-silco immune simulation. Our vaccine construct demonstrated good solubility, stability, antigenicity, non-allergenicity and non-toxicity with potential to elicit strong immune responses. However, further experimental research is needed to validate the safety and efficacy of the designed vaccine.