| Summary: | Foot-and-mouth disease virus (FMDV) causes a highly contagious and devastating disease in livestock animals and has a great potential to cause severe economic loss worldwide. The major antigen of FMDV capsid protein, VP1, contains the major B-cell epitope responsible for effectively eliciting protective humoral immunity. In this study, irradiated <i>Salmonella</i> Typhimurium (KST0666) were used as transgenic vectors containing stress-inducible plasmid pRECN-VP1 to deliver the VP1 protein from FMDV-type A/WH/CHA/09. Mice were orally inoculated with ATOMASal-L3 harboring pRECN-VP1, and FMDV virus-like particles, where (VLP<sub>FMDV</sub>)-specific humoral, mucosal, and cellular immune responses were evaluated. Mice vaccinated with attenuated <i>Salmonella</i> (KST0666) expressing VP1 (named KST0669) showed high levels of VLP-specific IgA in feces and IgG in serum, with high FMDV neutralization titer. Moreover, KST0669-vaccinated mice showed increased population of IFN-γ (type 1 T helper cells; Th1 cells)-, IL-5 (Th2 cells)-, and IL-17A (Th17 cells)-expressing CD4<sup>+</sup> as well as activated CD8<sup>+</sup> T cells (IFN-γ<sup>+</sup>CD8<sup>+</sup> cells), detected by stimulating VLP<sub>FMDV</sub>. All data indicate that our <i>Salmonella</i> vector system successfully delivered FMDV VP1 to immune cells and that the humoral and cellular efficacy of the vaccine can be easily evaluated using VLP<sub>FMDV</sub> in a Biosafety Level I (BSL1) laboratory.
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