VACCINES HAVE BEEN AN UNQUALIFIED SUCCESS FOR PREVENTING, CONTROLLING AND REDUCING THE ECONOMIC IMPACT OF MANY INFECTIOUS DISEASES OF ANIMALS. HISTORICALLY, LIVE ATTENUATED VACCINES (LAV) HAVE BEEN REGARDED AS THE MOST EFFICACIOUS VACCINES FOR VETERINARY APPLICATIONS DUE TO THEIR PERCEIVED ABILITY TO ELICIT STRONG PROTECTIVE IMMUNE RESPONSES FOLLOWING A SINGLE IMMUNIZATION. HOWEVER, IN MANY CASES, SIGNIFICANT ISSUES OF LAV SAFETY, EFFICACY, FORMULATION AND UTILITY REMAIN UNRESOLVED. IMPROVED VACCINES ADDRESSING THESE OUTSTANDING ISSUES ARE NEEDED TO MEET BOTH EXISTING AND NEW DISEASE CONTROL CHALLENGES.VIRAL VECTORED VACCINES (VVV) BASED ON ENGINEERED ATTENUATED OR HOST RANGE RESTRICTED VIRUSES HAVE BEEN DEVELOPED TO IMPROVE UPON EXISTING (LAV). COST ANALYSIS OF CURRENTLY AVAILABLE AND NEWLY DEVELOPED VVV SUGGESTS THEY MAY OFFER A COST-EFFECTIVE ALTERNATIVE FOR VACCINE PRODUCTION AND DISEASE CONTROL. NOTABLY, VVV ARE NOT AVAILABLE COMMERCIALLY FOR CATTLE AND OTHER NON-AVIAN PRODUCTION ANIMALS EVEN THOUGH COMPELLING POTENTIAL APPLICATIONS EXIST, FOR EXAMPLE IMPROVED VACCINES FOR BOVINE RESPIRATORY DISEASE (BRD).IN THIS PROPOSAL, WE WILL EVALUATE TWO NOVEL VIRAL VECTOR CANDIDATES WITH ADVANTAGEOUS FEATURES NOT FOUND IN OTHER VECTORS FOR USE IN CATTLE, THE PARAPOXVIRUS BOVINE PAPULAR STOMATITIS VIRUS (BPSV) AND THE GAMMA HERPESVIRUS BOVINE HERPESVIRUS 6 (BHV-6). BOTH OF THESE VIRUSES ARE UBIQUITOUS IN CATTLE POPULATIONS AND HAVE EVOLVED HIGHLY DESIRABLE INFECTION TRAITS THAT SHOULD TRANSLATE INTO VIRAL VECTORS WITH ENHANCED SAFETY, EFFICACY AND UNPARALLELED UTILITY IN CATTLE.WE ANTICIPATE THAT COMPLETION OF THESE STUDIES WILL HAVE BROAD SCIENTIFIC AND TRANSLATIONAL IMPACT; THEY WILL ADVANCE A NOVEL VACCINE VECTOR CONCEPT AND CLEARLY DEFINE THE POTENTIAL FOR BPSV- AND BHV-6-BASED VACCINE VECTORS FOR USE IN CATTLE. VIRAL VECTORS WITH THE POTENTIAL TO ENCODE MULTIPLE FOREIGN ANTIGENS WOULD BE IDEALLY SUITED FOR USE WITH BRD, A MULTI-PATHOGEN DISEASE WHERE MUCOSAL IMMUNITY PLAYS A HIGHLY SIGNIFICANT ROLE IN PROTECTION. ADDITIONALLY, SUCCESS WITH BPSV AND BHV-6 WILL LIKELY ENERGIZE DESIGN EFFORTS FOR ADDITIONAL VECTORED VACCINES FOR USE IN CATTLE, OTHER PRODUCTION ANIMAL SPECIES AND WILDLIFE.