** 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 (AI) IS AMONG THE MOST ECONOMICALLY IMPORTANT DISEASES AFFECTING POULTRY AND POSES A SIGNIFICANT THREAT TO THE SUSTAINABILITY OF THE POULTRY INDUSTRY WORLDWIDE. OVER THE PAST TWO DECADES, OUTBREAKS OF AI, ESPECIALLY INVOLVING HIGHLY PATHOGENIC AVIAN INFLUENZA (HPAI), HAVE CAUSED SEVERE ECONOMIC LOSSES IN MANY COUNTRIES, INCLUDING THE UNITED STATES (U.S.). NOTABLY, THE SPREAD OF HPAI IN THE U.S. IN 2014-2015 AFFECTED 50 MILLION DOMESTIC BIRDS AND RESULTED IN AN ESTIMATED LOSS OF $3.3 BILLION. CURRENTLY, THE U.S. HAS BEEN FACING ANOTHER DEVASTATING OUTBREAK OF HPAI THAT BEGAN IN 2022 AND AS OF AUGUST 3, 2023 HAS AFFECTED 58.7 MILLION BIRDS IN 47 STATES, SURPASSING THE PREVIOUS RECORD OF 2014-2015 OUTBREAKAND STANDING OUT AS THE MOST SIGNIFICANT ANIMAL DISEASE EVENT IN THE HISTORY OF THE U.S.VACCINATION IS THE MOST COST-EFFECTIVE AND HUMANE METHOD FOR THE CONTROL AND PREVENTION OF VIRAL DISEASES IN LIVESTOCK AND POULTRY. HOWEVER, VIRUSES LIKE AVIAN INFLUENZA VIRUS (AIV), WHICH ARE CONSTANTLY MUTATING, REQUIRE VACCINE PLATFORM(S) THAT CAN BE RAPIDLY DEVELOPED AND DEPLOYED IN RESPONSE TO EMERGING STRAINS. THUS, FLEXIBLE VACCINE PLATFORMS THAT ENABLE RAPID UPDATES ON AIV ANTIGENS TO MATCH CIRCULATING VIRUSES IN ENDEMIC AREAS OR NEWLY EMERGING VIRUSES IN NON-ENDEMIC COUNTRIES ARE NEEDED. WE WILL TACKLE THIS PROBLEMS BY DEVELOPING NOVEL VACCINE DELIVERY PLATFORMS FOR HPAI BASED ON A NEW CONDORPOX VIRUS VECTOR AND ON A SELF-AMPLIFYING RNA TECHNOLOGY PLATFORM. ADDITIONALLY, WE WILL ALSO DEVELOP SEROLOGICAL ASSAYS THAT WILL ENABLE DIFFERENTIATION OF VACCINATED FROM INFECTED ANIMALS. THE OUTCOMES OF THE PROPOSED PROJECT WILL HAVE A SIGNIFICANT IMPACT ON ANIMAL HEALTH AND ON THE SUSTAINABILITY OF THE POULTRY INDUSTRY WORLDWIDE.