INFLUENZA A VIRUS OF SWINE (IAV-S) IS WIDESPREAD IN THE SWINE POPULATION AND CAN CAUSE SIGNIFICANT ECONOMIC LOSS TO SWINE PRODUCERS. IAV-S VACCINES HAVE BEEN COMMONLY USED FOR CONTROL OF IAV-S IN THE US. UNFORTUNATELY THE EFFICACY OF THE CURRENTLY AVAILABLE VACCINES IS FAR FROM SATISFACTORY. THE MAIN LIMITATION IS THE THAT CURRENT VACCINES DO NOT CONFER ADEQUATE LEVELS OF PROTECTION DUE TO THE SUBSTANTIAL GENETIC DIVERSITY OF IAV-S CIRCULATING IN THE FIELD. THE ULTIMATE GOAL OF THIS PROPOSED RESEARCH IS TO DEVELOP A NOVEL VACCINE AGAINST IAV-S THAT WOULD ELICIT THE BROADEST LEVEL OF PROTECTION.WE WILL PURSUE A TWO-PRONGED APPROACH TO ACHIEVE THIS GOAL. FIRST WE WILL EMPLOY COMPUTATIONAL METHODS TO RATIONALLY DESIGN CONSENSUS IAV-S HEMAGGLUTININ (HA) IMMUNOGENS WITH THE BROADEST ANTIGENIC COVERAGE FOR THE IAV-S CIRCULATING IN THE US. SECOND WE WILL USE A NOVEL TRI-SEGMENTED PICHINDE VIRUS PICV-BASED VIRAL VECTOR TO DELIVER THE CONSENSUS HA IMMUNOGENS IN VACCINATED PIGS. ONE OF THE ADVANTAGES OF THIS PICV VIRAL VECTOR IS THAT IT SPECIFICALLY DELIVERS THE TARGET IMMUNOGENS TO DENDRITIC CELLS (DCS) AND MACROPHAGES OWING TO IS ABILITY TO REPLICATE IN THESE TWO CELL TYPES.OUR WORKINGHYPOTHESISIS PIGS VACCINATED WITH THE RECOMBINANT PICV-VIRAL VECTOR EXPRESSING THE CONSENSUS HA IMMUNOGENS WILL DEVELOP ROBUST LEVELS OF BROADLY PROTECTIVE IMMUNITY THAT WILL PROTECT THEM AGAINST DIVERGENT IAV-S STRAINS.SUCCESSFUL COMPLETION OF THIS PROJECT WILL SWINE PRODUCERS WITH AN EFFECTIVE TOOL TO REDUCE THE POTENTIAL ECONOMIC IMPACT OF IAV-S THEREBY ENHANCING THE SUSTAINABILITY AND COMPETITIVE ADVANTAGE OF THE US SWINE INDUSTRY.