In Silico design of multi-epitope vaccines against the foot and mouth disease virus (FMDV) structural protein (P1) region of serotype O by integrated structural vaccinology and molecular modeling approaches
摘要
Foot-and-mouth disease (FMD) is a highly contagious viral infection affecting cloven-hoofed livestock, caused by FMD viruses (FMDV). FMD is classified as a category A Transboundary Animal Disease (TAD) and is widespread globally. Pakistan is being a endemic region due to its dense agricultural livestock population. Currently, there are no effective vaccines or treatments for FMDV, which highlights an urgent need for research to develop appropriate therapeutic options for this disease. Computational vaccine design is a precise, efficient, and cost-effective method for developing effective vaccines against various diseases. In this study, we identified and selected a highly antigenic protein (P1) from the proteome of FMDV. Then, we selected highly antigenic epitopes to develop a next-generation multi-epitope vaccine construct. We incorporated a highly antigenic and stable adjuvant with immune epitopes (T-cell, B-cell, and HTL) to create the Structural Protein- Vaccine constructs, which demonstrate enhanced antigenicity, non-allergenicity, and favorable physicochemical properties. Additionally, 3D structure predictions and docking analyses indicated strong interactions with the animal Toll-like receptor 3 (TLR3), facilitating immune activation. In-silico cloning yielded CAI values of 1.0 with GC contents of 62.61%. Immune stimulation following three vaccine doses showed significant increases in IgG, IgM, interleukins, and cytokines, along with enhanced antigen clearance over time following the vaccine and two booster doses. Our vaccines against FMDV demonstrated high immunogenicity, eliciting a strong immune response requiring experimental clinical application validation.