Induction of a protective response in swine vaccinated with DNA encoding foot-and-mouth disease virus empty capsid proteins and the 3D RNA polymerase

This work focuses on the development of a potential recombinant DNA vaccine against foot-and-mouth disease virus (FMDV). Such a vaccine would have sig nificant advantages over the conventional inactivated virus vaccine, in par ticular having none of the risks associated with the high security requirem ents for working with live virus. The principal aim of this strategy was to stimulate an antibody response to native, neutralizing epitopes of empty F MDV capsids generated in vivo. Thus, a plasmid (pcDNA3.1/P1 -2A3C3D) was co nstructed containing FMDV cDNA sequences encoding the viral structural prot ein precursor P1-2A and the non-structural proteins 3C and 3D. The 3C prote in was included to ensure cleavage of the P1-2A precursor to VPO, VP1 and V P3, the components of self-assembling empty capsids, The non-structural pro tein 3D was also included in the construct in order to provide additional s timulation of CD4(+) T cells. When swine were immunized with this plasmid, antibodies to FMDV and the 3D polymerase were synthesized, Furthermore, neu tralizing antibodies were detected and, after three sequential vaccinations with DNA, some of the animals were protected against challenge with live v irus. Additional experiments suggested that the antibody response to FMDV p roteins was improved by the co-administration of a plasmid encoding porcine granulocyte-macrophage colony-stimulating factor, Although still not as ef fective as the conventional virus vaccine, the results encourage further wo rk towards the development of a DNA vaccine against FMDV.