Structurally modified master seed viruses to enhance conventional foot-and- mouth disease virus vaccine production.

The current FMD vaccines are inactivated whole virus preparations. Despite success in the developed world, two major problems limit their capacity to control infections in developing countries. First, the virus is notoriously unstable, especially for the serotypes O and SAT2. During production the manufacturer has to compensate for this instability, which is expensive and reduces vaccine yield. Also, unstable vaccines are believed to be less immunogenic due to degradation before and after inoculation. In addition, to be effective, FMDV vaccines require frequent booster vaccinations, possibly due to vaccine antigen instability. Secondly, FMDV serotypes can be highly variable, especially serotypes A and SAT2, necessitating frequent development of new vaccine strains. Some viruses have proven very difficult to adapt to cell culture, slowing the manufacturing process, reducing vaccine yield and potentiating the selection of undesired antigenic changes. The main objectives of this proposal are to use reverse genetics to produce and market, on an industrial scale, recombinant FMD viruses with enhanced thermal stability and cell-culture growth. Currently, live recombinant viruses can be recovered and inactivated vaccine produced in the conventional manner. However, the feasibility of applying this technology on an industrial scale has not yet been tested.