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

Abstract

This work focuses on the development of a potential recombinant DNA vaccine against foot-and-mouth disease virus (FMDV). Such a vaccine would have significant advantages over the conventional inactivated virus vaccine, in particular having none of the risks associated with the high security requirements for working with live virus. The principal aim of this strategy was to stimulate an antibody response to native, neutralizing epitopes of empty FMDV capsids generated in vivo. Thus, a plasmid (pcDNA3.1/P1–2A3C3D) was constructed containing FMDV cDNA sequences encoding the viral structural protein precursor P1–2A and the non-structural proteins 3C and 3D. The 3C protein was included to ensure cleavage of the P1–2A precursor to VP0, VP1 and VP3, the components of self-assembling empty capsids. The non-structural protein 3D was also included in the construct in order to provide additional stimulation of CD4+ T cells. When swine were immunized with this plasmid, antibodies to FMDV and the 3D polymerase were synthesized. Furthermore, neutralizing antibodies were detected and, after three sequential vaccinations with DNA, some of the animals were protected against challenge with live virus. Additional experiments suggested that the antibody response to FMDV proteins was improved by the co-administration of a plasmid encoding porcine granulocyte–macrophage colony-stimulating factor. Although still not as effective as the conventional virus vaccine, the results encourage further work towards the development of a DNA vaccine against FMDV.