VACCINES ARE THE MOST EFFECTIVE STRATEGY FOR PREVENTION AND CONTROL OF LIVESTOCK INFECTIOUS DISEASES, AND VIRAL VECTORS ARE AMONGTHE MOST PROMISING PLATFORMS TO ADMINISTER THE NEXT-GENERATION OF VETERINARY VACCINES. VIRAL VACCINE DELIVERY SYSTEMS THAT HAVEBEEN DEVELOPED AND ARE CURRENTLY IN USE IN VETERINARY MEDICINE, INCLUDE POXVIRUSES, HERPESVIRUSES, ALPHAVIRUSES ANDPARAMYXOVIRUSES. THEIR EFFECTIVENESS IS BASED ON THE ABILITY OF THE VECTOR TO INDUCE BOTH ARMS OF THE IMMUNE SYSTEM RESULTING INTHE PRODUCTION OF ANTIBODIES AND CELLULAR CELLULAR IMMUNE RESPONSES IN TARGET ANIMAL SPECIES. ADDITIONALLY, VECTORED VACCINES AREUSUALLY SAFER THAN MODIFIED LIVE VACCINES, AND MOST VIRAL VECTORS OFFER A FLEXIBLE PLATFORM THAT CAN BE RAPIDLY ENGINEERED INTONOVEL VACCINE CANDIDATES.THE GOAL OF THE STUDY PROPOSED HERE IS TO DEVELOP A MULTI-SPECIES VECTOR PLATFORM FOR VACCINE DELIVERY IN CATTLE AND SWINE.SPECIFIC AIMS OF THE STUDY ARE: 1) TO DEVELOP AN ORFV-BASED VECTOR PLATFORM WITH ENHANCED IMMUNOGENICITY AND SAFETY,2) TO CONSTRUCT RECOMBINANT ORFV VECTORS EXPRESSING PROTECTIVE ANTIGENS OF IMPORTANT PATHOGENS OF CATTLE AND SWINE,AND 3) TO EVALUATE THE IMMUNOGENICITY AND PROTECTIVE EFFICACY OF ORFV-BASED RECOMBINANT VECTORS IN TARGET ANIMALSPECIES. A NOVEL VECTOR PLATFORM BASED ON THE RECENTLY CHARACTERIZED AND HIGHLY IMMUNOGENIC PARAPOXVIRUS ORF VIRUS WILL BEDEVELOPED HERE. BY USING TRADITIONAL VIRAL GENETIC ENGINEERINF APPROACHES A GENE THAT CONTRIBUTES TO THE PATHOGENICITY OF ORFVWILL BE REMOVED FROM THE ORFV GENOME. THIS PLATFORM WILL BE USED TO GENERATE RECOMBINANT VECTORS EXPRESSING THE PROTECTIVEANTIGENS OF IMPORTANT VIRAL PATHOGENS OF CATTLE (BOVINE HERPESVIRUS 1, BOHV-1) AND SWINE (SWINE INFLUENZA VIRUS, SIV). ADDITIONALEXPERIMENTAL APPROACHES WILL INCLUDE EVALUATION OF THE IMMUNOGENICITY AND PROTECTIVE EFFICACY OF THE ORFV VECTOR PLATFORMFOLLOWING IMMUNIZATION-CHALLENGE EXPERIMENTS IN TARGET ANIMAL SPECIES. SEROLOGICAL AND CELL MEDIATED IMMUNE RESPONSESELICITED BY IMMUNIZATION WITH ORFV VECTORS WILL BE ASSESSED BY QUANTIFYING ANTIGEN/VIRUS SPECIFIC ANTIBODY LEVELS CELL EFFECTORAND MEMORY RESPONSES BY FLOW CYTOMETRY, RESPECTIVELY.THE PROPOSED WORK WILL HAVE A SIGNIFICANT IMPACT ON ANIMAL HEALTH BY PROVIDING A SAFE AND HIGHLY IMMUNOGENIC VACCINE DELIVERYPLATFORM FOR INFECTIOUS DISEASE PREVENTION AND CONTROL IN LIVESTOCK SPECIES. AVAILABILITY OF A MULTI-SPECIES VACCINE DELIVERYPLATFORM THAT ALLOWS RAPID GENERATION OF NOVEL VECTORED VACCINE CANDIDATES MAY BE HIGHLY EFFECTIVE TO COMBAT ENDEMIC, NEWLY- ORRE-EMERGING INFECTIOUS DISEASES THAT CURRENTLY THREATEN OR MAY BECOME A THREAT TO THE US LIVESTOCK INDUSTRY.