Immunoinformatics-Driven Multi-Epitope Vaccine Design for Foot-and-Mouth Disease Virus

Foot-and-mouth disease (FMD) is the most destructive for livestock with reservoirs in cattle, buffalo, sheep, goats, and pigs and foot-and-mouth disease virus (FMDV) with seven serotypes. Current vaccination strategies suffer from difficulties with antigenic variability coupled with high costs. This paper aims to design a multi-epitope subunit vaccine against FMDV by the use of immunoinformatics approach in order to improve effectiveness. We used immunoinformatics to design a subunit vaccine that included two T-cell epitopes linked with AAV and three B-cell epitopes linked with KK. T- and B-cell epitopes were joined by a GPSL linker. A Pan HLA-DR binding epitope, PADRE, was attached at both ends using EAAAK linkers. Physicochemical properties, allergenicity, and antigenicity of the vaccine were evaluated, along with secondary and tertiary structure predictions and molecular docking studies with the Toll-like receptor 9 (TLR-9). The vaccine had a predicted to be non-allergic and with high antigenic property (0.73). Physicochemical analysis showed to be 135 amino acids, stable (21.29 stability index), and basic (pI of 10.51). The overall 3D structure showed robust binding affinity against the cattle TLR-9 receptor. It was confirmed, in silico cloning, effective transformation into prokaryotic expression vector pET-28a (+). The subunit vaccine developed based on immunoinformatics has great promise in the form of a high antigenicity level, stabilized physicochemical properties, and interactions well-favored with TLR-9. This indicates potential further experimental validation of effectiveness as a candidate vaccine against FMD.