** AWARDS ISSUED PRIOR TO JANUARY 20, 2025, WERE FUNDED UNDER PREVIOUS ADMINISTRATIONS AND MAY NOT REFLECT THE PRIORITIES AND POLICIES OF THE CURRENT ADMINISTRATION.** AVIAN INFLUENZA POSES A SERIOUS THREAT TO GLOBAL POULTRY HEALTH AND FOOD SECURITY. CURRENT VACCINES AGAINST THE PREVALENT H9N2 SUBTYPE ARE INADEQUATE, NECESSITATING INNOVATIVE APPROACHES. OUR RESEARCH AIMS TO DEVELOP EFFECTIVE MASS VACCINATION STRATEGIES USING MODIFIED LIVE ATTENUATED VACCINES (MLVS).THIS PROJECT WILL ANALYZE THE GENETIC MAKEUP OF THE H9N2 VIRUS TO UNDERSTAND ITS EVOLUTION AND IDENTIFY KEY TARGETS FOR VACCINE DEVELOPMENT. WE WILL CREATE AND TEST IMPROVED MLVS, ENSURING THEIR SAFETY AND EFFECTIVENESS IN PREVENTING DISEASE TRANSMISSION. ADDITIONALLY, WE WILL EXAMINE HOW THESE MLVS STIMULATE THE IMMUNE SYSTEM COMPARED TO TRADITIONAL VACCINES, FOCUSING ON MUCOSAL, HUMORAL, AND CELLULAR RESPONSES.OUR FINDINGS WILL SIGNIFICANTLY ENHANCE OUR UNDERSTANDING OF THE H9N2 VIRUS AND PROVIDE VALUABLE TOOLS FOR RAPIDLY ASSESSING NEW STRAINS. THIS KNOWLEDGE WILL DIRECTLY CONTRIBUTE TO THE DEVELOPMENT OF MORE EFFECTIVE VACCINES AGAINST AVIAN INFLUENZA, NOT ONLY USING MLVS BUT ALSO OTHER VACCINE TECHNOLOGIES.THIS INNOVATIVE APPROACH IS A DEPARTURE FROM TRADITIONAL METHODS AND COULD REVOLUTIONIZE POULTRY VACCINATION. THE POTENTIAL BENEFITS EXTEND BEYOND AVIAN INFLUENZA, PAVING THE WAY FOR SIMILAR STUDIES ON OTHER RESPIRATORY VIRUSES AFFECTING POULTRY AND LIVESTOCK. BY ADDRESSING THE LIMITATIONS OF CURRENT VACCINES AND DEVELOPING SAFER, MORE EFFECTIVE ALTERNATIVES,WE CAN PROTECT ANIMAL HEALTH, SAFEGUARD THE FOOD SUPPLY, AND MITIGATE THE ECONOMIC IMPACT OF AVIAN INFLUENZA OUTBREAKS.