Foot-and-mouth disease (FMD) is an extremely contagious viral disease of a variety of wild and domestic cloven-hoofed animals, including pigs. The disease is distributed worldwide and has great negative economic impact not only on livestock health and production but also on international trade. The constant presence of outbreaks in many regions of the world highlights the potential of accidental or deliberate introductions of FMD in the U.S. The current FMD vaccine is a formulation of inactivated whole virus and adjuvant that requires 7 days to induce protection, a time during which vaccinated animals are still susceptible to disease. Therefore, it is essential to develop new control strategies that could confer very early protection and stop disease spread. Attenuated vaccines are expected to elicit more rapid and a long lived immunity and at the same time could be an excellent tool to study the interactions between viruses and the host in detail. Indeed, some viral diseases have been eradicated using live-attenuated vaccines (i.e. Rinderpest and Smallpox). Our goal is to develop new FMD control strategies including novel attenuated vaccine candidates.
In the last couple of years with the support of NPB we have derived a mutant strain of FMDV A12 that did not cause disease in swine (so-called FMDV-SAP mutant) and induced a strong immune response protecting animals from challenge, as early as two days post vaccination. However in rare occasions, revertants with increased virulence spontaneously arose. Here we report the characterization of new FMDV mutants where we have incorporated additional changes in the Leader and other viral proteins to address reversion to virulence and at the same time to add genetic markers for differentiating infected from vaccinated animals. These mutant strains have the potential for further development into novel live attenuated vaccine candidates to improve immunity against FMD.