** AWARDS ISSUED PRIOR TO JANUARY 20, 2025, WERE FUNDED UNDER PREVIOUS ADMINISTRATIONS AND MAY NOT REFLECT THE PRIORITIES AND POLICIES OF THE CURRENT ADMINISTRATION.** INFLUENZA A VIRUSES (IAV) ARE IMPORTANT RESPIRATORY PATHOGENS THAT IMPACT ANIMAL AND PUBLIC HEALTH. A DIVERSE RANGE OF IAVS CO-CIRCULATE IN SWINE GLOBALLY, WITH SUBSTANTIAL DIFFERENCES BETWEEN THEM, COMPLICATING THE DIAGNOSIS AND CONTROL OF INFLUENZA IN PIGS. ALTHOUGH INFLUENZA IN SWINE IS USUALLY MILD, IT CAN RESULT IN SUBSTANTIAL ECONOMIC BURDEN. VACCINATION REMAINS THE MOST EFFECTIVE METHOD TO PROTECT PIGS AGAINST INFLUENZA INFECTION AND/OR DISEASE AND IS ROUTINELY USED BY U.S. SWINE PRODUCERS AND VETERINARIANS. TRADITIONAL INACTIVATED VACCINES USED FOR PIGS CONFER STRONG PROTECTION AGAINST MATCHED VIRUSES BUT LITTLE PROTECTION IN CASE OF MISMATCHED VIRUSES. ALTHOUGH VACCINES HAVE AN IMPORTANT ROLE IN THE CONTROL OF INFLUENZA IN SWINE, REPEATED FAILURES AND THE NEED FOR CONSTANT UPDATES HIGHLIGHT THE NEED FOR BETTER, MORE EFFECTIVE APPROACHES. LIVE ATTENUATED INFLUENZA VIRUS (LAIV) VACCINES HAVE AN ADVANTAGE OVER TRADITIONAL INACTIVATED PRODUCTS BECAUSE THEY MIMIC A NATURAL INFECTION AND ELICIT A COMBINATION OF ANTIBODY AND CELL-MEDIATED IMMUNE RESPONSES. A RECENTLY APPROVED LAIV VACCINE FOR USE IN PIGS HAS RAISED CONCERNS ABOUT THE SAFETY OF LIVE VACCINES IN SWINE. HOWEVER, THE ADVANTAGES FOR THE USE OF LIVE VACCINES AND THE TRACK-RECORD OF SAFETY AND SUCCESSFUL ERADICATION OR CONTROL PROGRAMS IN HUMANS AND ANIMALS STILL MAKE THEM A VALUABLE ALTERNATIVE FOR EFFECTIVE CONTROL OF INFLUENZA IN PIGS. THUS, THE MAJOR GOAL OF THIS APPLICATION IS TO DEVELOP LAIV VACCINE STRATEGIES THAT ARE NOT ONLY EFFECTIVE, BUT ALSO SHOW IMPROVED SAFETY AND LOWER ABILITY TO COMBINE WITH FIELD VIRUSES. WE WILL GENERATE SEVERAL LAIV VACCINE CANDIDATES AND TEST THEIR SAFETY IN CULTURED CELLS AND IN PIGS. ADDITIONALLY, WE WILL EVALUATE THE IMMUNE RESPONSE STIMULATED BY THE DIFFERENT VACCINE CANDIDATES IN PIGS. THE VACCINE CANDIDATE THAT STIMULATES THE STRONGEST IMMUNE RESPONSE WILL THEN BE TESTED FOR PROTECTION AGAINST INFLUENZA VIRUS INFECTION IN PIGS. THROUGH THE PROPOSED RESEARCH, WEEXPECT TO GENERATE AND DEMONSTRATE THAT THE MODIFIED LAIVS ARE SAFE AND EFFECTIVE IN PROTECTING PIGS AGAINST INFLUENZA AND REPRESENT AN EFFICIENT ALTERNATIVE TO BE USED BY THE SWINE INDUSTRY.