A novel immunoinformatics approach for developing a poly-epitope vaccine targeting foot and mouth disease virus, exploiting structural VP proteins

Abstract

Foot and mouth Disease virus (FMDV) belongs to Picornaviridae family and Aphthovirus genus causing Foot and mouth disease (FMD) in cloven-hoofed animals. FMDV, a prevalent virus induces both acute and chronic infections with high mutation rates resulting in seven primary serotypes, making vaccine development indispensable. Due to time and cost effectiveness of the immunoinformatic approach, we designed in-silico polyepitope vaccine (PEV) for the curtailment of FMDV. Structural and immunogenic parts of FMDV (Viral Protein 1 (VP1), Viral Protein 2 (VP2), Viral Protein 3 (VP3), and Viral Protein 4 (VP4)) were used to design the cytotoxic T Lymphocyte (CTL), Helper T Lymphocyte (HTL), and B-cell epitopes, followed by screening for antigenic, non-allergenic, Interferon (IFN) simulator, and non-toxicity, which narrowed down to 7 CTL, 3 HTL, and 12 B-cell epitopes. These selected epitopes were linked using appropriate linkers and Cholera Toxin B (CTB) adjuvant for immunological modulation. The physiochemical analyses followed by the structure prediction demonstrated the stability, hydrophilicity and solubility of the PEV. The interactions and stability between the vaccine, Toll like Receptor 3 (TLR3) and Toll like receptor 7 (TLR7) were revealed by molecular docking and Molecular Mechanics/Poisson Boltzmann Surface Area (MMPBSA) with high stability and compactness verified by MD simulation. In-silico immune simulation demonstrated a strong immunological response. FMDV-PEV (Poly epitope vaccine) will be effectively produced in an E. coli system, as codon optimization and cloning in an expression vector was performed. The effectiveness, safety, and immunogenicity profile of FMDV-PEV may be confirmed by further experimental validations.Communicated by Ramaswamy H. Sarma.

Keywords: FMDV; Immunoinformatics; computational biology; immunogenicity; polyepitope; vaccine.