Foot-and-mouth disease (FMD) is economically the most important viral-induced livestock disease worldwide. The disease is highly contagious and FMD virus (FMDV) replicates and spreads extremely rapidly. Outbreaks in previously FMD-free countries, including Taiwan, the United Kingdom, and Uruguay, and the potential use of FMDV by terrorist groups have demonstrated the vulnerability of countries and the need to develop control strategies that can rapidly inhibit or limit disease spread. The current
vaccine, an inactivated whole virus preparation, has a number of limitations for use in outbreaks in disease-free countries. We have developed an alternative approach using a genetically engineered FMD
subunit vaccine that only contains the portions of the viral genome required for virus capsid assembly and lacks the coding region for most of the viral nonstructural (NS)
proteins including the highly immunogenic 3D
protein. Thus, animals inoculated with this
marker vaccine can readily be differentiated from infected animals using diagnostic assays employing the NS
proteins not present in the
vaccine and production of this
vaccine, which does not contain infectious FMDV, does not require expensive high-containment manufacturing facilities. One inoculation of this
subunit vaccine delivered in a replication-defective human adenovirus vector can induce rapid, within 7 days, and relatively long-lasting protection in swine. Similarly cattle inoculated with one dose of this recombinant vector are rapidly protected from direct and contact exposure to virulent virus. Furthermore, cattle given two doses of this
vaccine developed high levels of FMDV-specific
neutralizing antibodies, but did not develop
antibodies against
viral NS proteins demonstrating the ability of FMD subunit vaccinated animals to be differentiated from infected animals. To stimulate early protection prior to the
vaccine-induced adaptive immune response we inoculated swine with the
antiviral agent,
type I interferon, and induced complete protection within 1 day. Protection can last for 3-5 days. The combination of the FMD
marker vaccine and
type I interferon can induce immediate, within 1 day, and long-lasting protection against FMD. Thus, this combination approach successfully addresses a number of concerns of FMD-free countries with the current disease control plan. By rapidly limiting virus replication and spread this strategy may reduce the number of animals that need to be slaughtered during an outbreak.