An integrated structural and immunoinformatic approach to design a multi-epitope based vaccine against the foot-and-mouth disease virus

The Foot-and-mouth disease virus (FMDV) is highly contagious, affecting cloven-hoofed animals and causing significant economic losses to the livestock industry. Its high genetic variability complicates vaccine development, necessitating frequent updates to traditional inactivated vaccines. Multi-epitope-based vaccines (MEBVs) offer a promising alternative by incorporating immunogenic epitopes to elicit robust humoral and cell-mediated immune responses, thereby providing broader protection against diverse FMDV strains. Using in silico approaches, we designed a novel FMDV-targeting MBEV specifically tailored to the BoLA alleles to ensure optimal epitope selection for cattle. The MEBV included non-toxic, antigenic, and non-allergenic epitopes combined with β-defensin 3 adjuvants, PADRE sequences, and linkers to enhance immunogenicity and stability. Molecular docking and dynamics simulations confirmed strong binding affinity and stable interactions with TLR3 and TLR7, and immune simulation analysis revealed notable increases in B-cell and T-cell populations, cytokines, and macrophages, with sustained levels of IFN-γ and IL-2. Codon optimization for Escherichia coli K12 enhanced expression, and in silico restriction cloning demonstrated its scalability for production. Our findings suggest that the MEBV design is a cost-effective and efficient approach to combat FMDV. While experimental validation is required, the in silico results also highlight its potential to trigger protective immune responses and address the limitations of traditional vaccines.