CLASSICAL SWINE FEVER (CSFV), PORCINE CIRCO AND PSUDORABIES VIRUSES (CSFV, PCV AND PRV) ARE IMPORTANT SWINE VIRAL DISEASES WORLDWIDE. BOTH CSFV AND PRV HAVE BEEN ERADICATED IN COMMERCIAL SWINE IN THE U.S. AND MANY EUROPEAN COUNTRIES. WHILE PRV IS ENDEMIC, PREVALENCE OF CSF IN WILD AND FERAL PIGS IN EUROPE IS SUSPECTED. IN 2000, THERE WAS AN OUTBREAK OF CSFV IN THE NORTHERN MEXICO DUE TO MOVEMENT OF PIGS FROM ENDEMIC AREAS OF SOUTHERN MEXICO. THEREFORE, THERE IS A CONSTANT RISK IN THE US OF PRV SPILLOVER FROM WILD/FERAL PIGS AND ACCIDENTAL CSFV INTRODUCTION. VACCINATION AGAINST PRV AND CSFV IS NOT ALLOWED IN EUROPE AND US BECAUSE OF VACCINE SAFETY AND ASSOCIATED COMPLICATIONS. PCV2 VIRUS BY ITSELF DOES NOT CAUSE A CLINICAL DISEASE. HOWEVER, IN PCV2-INFECTED PIGS, THE PATHOGENICITY OF OTHER VIRAL INFECTIONS IS ENHANCED AND THE EFFICACY OF VACCINATION DECREASED. WE HAVE CONSTRUCTED A TRIPLE GENE MUTATED PRV (PRV TMV) AND DETERMINED ITS SAFETY AND IMMUNOGENICITY IN PIGS. PRV TMV IS SAFE IN PIGS AND INDUCED A RAPID NEUTRALIZING ANTIBODY RESPONSE IN VACCINATED PIGS. WE HAVE ENGINEERED THE PRV TMV FURTHER TO EXPRESS PCV2 CAPSID (CAP), CSF E2 AND A CHIMERIC ERNS PROTEIN BY FUSING WITH THE PORCINE GRANULOCYTE MACROPHAGE COLONY STIMULATING FACTOR (GMCSF). IN THE CURRENT PROPOSAL, WE WILL DETERMINE THE LATENCY-REACTIVATION PROPERTY OF PRV TMV, DETERMINE A SUITABLE VACCINE DOSE AND FINALLY DETERMINE THE PROTECTION OF VACCINATED PIGS AGAINST A PCV2B (LSU) AND A VIRULENT CSFV (PLUM ISLAND) CHALLENGE. IF SUCCESSFUL, THE PRV TMV VECTORED BIVALENT CSFV/PCV2B SUBUNIT VACCINE COULD REPLACE THE PESTIVIRUS CHIMERA "CP7_E2ALF" (SUVAXYN CSF MARKER, ZOETIS), WHICH IS CURRENTLY LICENSED IN THE EU COUNTRIES FOR VACCINATION OF PIGS IN THE CASE OF A CSFV OUTBREAK. THE CP7_E2ALF CHIMERA PROTECTS PIG AGAINST CSFV BUT THE FEAR IS THAT WHILE SOLVING THE PROBLEM IN PIGS, IT MAY CREATE A SERIOUS PROBLEM FOR THE CATTLE INDUSTRY. THE CP7_E2ALF IS A CYTOPATHIC BVDV STRAIN THAT HAS BEEN ENGINEERED TO EXPRESS CSFV E2 INSTEAD OF BVDV E2. THE THOUGHT IS THAT CIRCULATION OF CP7_E2ALF MAY GIVE RISE TO A HIGHLY PATHOGENIC BVDV STRAIN. THEREFORE, COMPLETION OF THIS PROJECT WILL BENEFIT THE PIG INDUSTRY WORLDWIDE AND WILL GIVE THE US CATTLE INDUSTRY A PIECE OF MIND.