AVIAN INFLUENZA VIRUS (AIV) IS A DEVASTATING DISEASEWITH DEMONSTRATED ABILITY TO CAUSE THE LOSS OF HUNDREDS OF MILLIONS OF BIRDS.THE MAJOR GOAL OF THIS PROJECT IS TOTEST THE HYPOTHESIS THAT MODIFIED LIVE VIRUS (MLV) VACCINESINDUCE GREATER AND MORE BROADLY REACTIVE IMMUNE RESPONSES AND PROVIDE SUPERIOR PROTECTION THAN STANDARD INACTIVATED VACCINES AGAINST AVIAN INFLUENZA.THE POULTRY INDUSTRY, COMPRISING OF BILLIONS OF BIRDS, IS OF HUGE ECONOMIC AND SOCIAL IMPORTANCE THROUGHOUT THE WORLD. IN SOME COUNTRIES, VACCINATION HAS BEEN INTRODUCED TO PREVENT AIV OUTBREAKS; HOWEVER,CURRENT VACCINES OFFERLIMITED PROTECTION AND CANNOT PREVENT THE SPREAD OF THE VIRUS. NOWADAYS, THE WORLD CONFRONTS ANUNPRECEDENTED SPREAD OFAIVS IN POULTRY INASIA, THE MIDDLE EAST AND AFRICA, WITH FREQUENT SPILL OVER ANDTRANSCONTINENTAL SPREAD OF THESE VIRUSES THROUGH MIGRATORY BIRDS TO OTHER PARTS OF THE WORLD, INCLUDING THE U.S. THUS, IT IS ABSOLUTELY ESSENTIALTO BETTER UNDERSTANDTHE MECHANISMS INVOLVED IN VACCINE IMMUNOGENICITY AND TODEVELOPALTERNATIVE VACCINATION STRATEGIES THAT CAN MORE EFFECTIVELY CONTRIBUTE TO PREVENT AND CONTROL OF AIV.WE ARE A STRONG COLLABORATIVE TEAM WITH EXPERTISE IN INFLUENZA VIRUS REVERSE GENETICS, AVIAN IMMUNOLOGY AND AVIAN MODELS OF INFLUENZA DISEASE TO DEVELOP MLV VACCINES AGAINSTAIVS FOR USE IN POULTRY. WE WILL COMPARE THE CHARACTERISTICS OF MLV VACCINESIN VITROANDIN VIVOAND EXAMINE SAFETY,TRANSMISSION POTENTIAL OF THE VACCINES TO SUSCEPTIBLE BIRDS, AND GENETIC VARIABILITY OF CHALLENGE VIRUSOUT OF VACCINATED VERSUS NON-VACCINATEDBIRDS.