** AWARDS ISSUED PRIOR TO JANUARY 20, 2025, WERE FUNDED UNDER PREVIOUS ADMINISTRATIONS AND MAY NOT REFLECT THE PRIORITIES AND POLICIES OF THE CURRENT ADMINISTRATION.** MYCOPLASMA OVIPNEUMONIAE IS A BACTERIUM THAT INFECTS SHEEP AND THAT CONTRIBUTES TO THE DEVELOPMENT OF RESPIRATORY DISEASES. THERE ARE CURRENTLY NO TREATMENTS OR VACCINES FOR THIS PATHOGEN. WE HAVE RECENTLY SHOWN THAT MYCOPLASMA OVIPNEUMONIAE CAN FORM BIOFILMS. BIOFILMS ARE COMMUNITIES OF BACTERIA THAT STICK TO EACH OTHER AND TO A SURFACE AND THAT THEREFORE ARE VERY RESISTANT TO TREATMENTS. WITH THIS PROJECT, WE SEEK TO DEVELOP AND TEST A NOVEL MYCOPLASMA OVIPNEUMONIAE VACCINE THAT TARGETS BIOFILMS IN THE RESPIRATORY TRACT TO CLEAR OR PREVENT MYCOPLASMA OVIPNEUMONIAE INFECTION. WE HYPOTHESIZE THAT INCLUDING MATERIAL FROM BIOFILMS IN THE VACCINE WILL LEAD TO A STRONG IMMUNE RESPONSE THAT CAN PREVENT THE FORMATION OF BIOFILMS OR BREAK UP EXISTING BIOFILMS. IN OUR PROJECT, WE WILL (1) DESIGN AND PRODUCE A VACCINE TO MYCOPLASMA OVIPNEUMONIAE THAT INCORPORATES BIOFILM COMPONENTS AND THAT INDUCES AN IMMUNE RESPONSE IN THE RESPIRATORY TRACT AND (2) TEST WHETHER A BIOFILM-BASED MYCOPLASMA OVIPNEUMONIAE VACCINE CAN PROTECT SHEEP FROM MYCOPLASMA OVIPNEUMONIAE INFECTION. AN EFFECTIVE VACCINE IS EXPECTED TO PREVENT INFECTION AND IMPROVE HEALTH AND PRODUCTIVITY OF LAMBS THAT ARE EXPERIMENTALLY OR NATURALLY EXPOSED TO MYCOPLASMA OVIPNEUMONIAE. IF THIS PROJECT IS SUCCESSFUL, FARMERS WILL FINALLY HAVE A TOOL TO COMBAT MYCOPLASMA OVIPNEUMONIAE INFECTION. IF WE CAN DEMONSTRATE THAT INCORPORATION OF BIOFILM MATERIAL IN A MYCOPLASMA VACCINE IS EFFECTIVE, THIS APPROACH COULD ALSO BE ADAPTED FOR OTHER PATHOGENIC MYCOPLASMA IN OTHER AGRICULTURAL SPECIES.