** AWARDS ISSUED PRIOR TO JANUARY 20, 2025, WERE FUNDED UNDER PREVIOUS ADMINISTRATIONS AND MAY NOT REFLECT THE PRIORITIES AND POLICIES OF THE CURRENT ADMINISTRATION.** DISEASES OF SWINE ARE CAUSED BY THE PRRS VIRUS (PRRSV). PRRSV CONTINUES TO DISTRESS THE GLOBAL PORK INDUSTRY BY CAUSING ECONOMIC LOSSES ESTIMATED AT $664 MILLION EVERY YEAR DUE TO REPRODUCTIVE FAILURE, FATAL RESPIRATORY DISEASE, AND SUBSEQUENT SECONDARY BACTERIAL INFECTION.SWINE INFLUENZA VIRUS (SIV) CAUSES ACUTE RESPIRATORY DISEASES IN BREEDING AND NURSERY PIGS AND CAN PREDISPOSE THE INFECTED ANIMALS TO SECONDARY VIRAL AND BACTERIAL INFECTIONS. IN ADDITION TO THE ADVERSE ECONOMIC IMPACT ON PIG PRODUCERS, SIV IS ALSO A ZOONOTIC PATHOGEN DETRIMENTAL TO HUMANS. COINFECTIONOF PIGS WITH PRRSV, PORCINE CIRCOVIRUS TYPE 2 (PCV2), AND SIV ON THE SAME FARMS ALSO PLAYS A CRITICAL ROLE IN THE PORCINE RESPIRATORY DISEASE COMPLEX AND IS FREQUENTLY REPORTED.SINCE THE LATE 1990S, KILLED AND MODIFIED LIVE VIRUS (MLV) PRRSV VACCINES BASED ON ATTENUATED EUROPEAN OR NORTH AMERICAN PRRSV STRAINS HAVE BEEN COMMERCIALIZED AND USED TO CONTROL PRRS. THE MLV-PRRS VACCINE HAS SAFETY ISSUES DUE TO THE PERSISTENCE OF THE VACCINE VIRUS IN THE HOST AND INCREASED MUTATION RATES. CONSEQUENTLY, VACCINE-LIKE VIRULENT PRRSV STRAINS HAVE EMERGED AND CAUSED VACCINE FAILURES INSTEAD OF PROTECTING THE PIGS. LIKEWISE, CURRENTLY AVAILABLE INACTIVATED SWINE INFLUENZA VACCINES ARE INEFFECTIVE IN CONTROLLING SIV IN PIGS DUE TO THE STRAIN VARIABILITY.PREVIOUSLY, WE DEVELOPED A QUADRUPLE GENE-DELETED PSEUDORABIES VIRUS (PRVQMV) VACCINE VECTOR PLATFORM IN WHICH ENVELOPE GLYCOPROTEIN GE, US9, GG, AND THYMIDINE KINASE (TK) GENES ARE DELETED. A CHIMERIC PCV2 CAPSID PROTEIN (CAP) WAS ALSO INSERTED, RESULTING IN THE PRVQMV-CAP.IN THIS PROJECT, OUR GOALS ARE TO ENGINEER THE PRVQMV FURTHER, I) TO INCORPORATE THE PRSSV ENVELOPE PROTEINS GLYCOPROTEINS (GP2.GP3,GP4, AND GP5) AND THE MATRIX PROTEIN, AND TEST ITS VACCINE PROTECTIVE EFFICACY AGAINST A VIRULENT PRRSV CHALLENGE STRAIN AND II) TO INCORPORATE THE SIV ENVELOPE GLYCOPROTEINS H1N1 AND H3N2, AND TEST ITS PROTECTIVE EFFICACY AGAINST THE TWO DIFFERENT (H1N1 AND H3N2 STRAINS) VIRULENT INFLUENZA CHALLENGE VIRUSES.