Abstract: Foot and Mouth Disease (FMD) is a highly infectious and economically devastating disease of livestock. A genetically engineered vaccine against Foot and Mouth Disease Virus (FMDV) may be a good control measure for use during an epidemic. In this study, a secretory expression vector, pPIC9K-VP1-2A-CTE, containing a fusion of the bovine (FMDV) type Asia 1 VP1-2A gene and a multi-epitope CTB-TEpi (CTE) was constructed. After being linearized with Sal I, the recombinant plasmid was transformed into Pichia pastoris GS115 by electroporation. The fusion protein expressed in yeast was analyzed by SDS-PAGE and Western blot and immunogenicity of the fusion protein was assessed. The expressed recombinant VP1-2A and CTE protein elicited specific humoral and cellular immune responses in mice. Additionally, immunized guinea pigs were protected when challenged with the FMD Asia 1 virus.