Foot-and-mouth disease virus (FMDV) causes a highly contagious disease of cloven-hoofed animals including swine, cattle, sheep and goats. The economic impact of an FMD outbreak can be devastating as demonstrated by the 1997 and 2001 outbreaks in Taiwan and the United Kingdom, respectively. Although an FMD vaccine is available, its use in the event of an outbreak in a previously FMD-free country such as the U.S. is uncertain because of a number of drawbacks. We have previously developed an subunit FMD vaccine that overcomes many of these limitations and recently combined this subunit vaccine with an antiviral approach, using interferon alpha, to induce very rapid protection. In this study we have demonstrated that delivery of the combination of our FMD subunit vaccine and interferon alpha can enhance the long-term protection afforded swine with the vaccine alone. Furthermore, we are developing additional antiviral reagents, ie., interferon beta, that may allow us to supplement our current approach as well as develop a more comprehensive understanding of the interactions between FMDV and its host.