**AWARDS ISSUED PRIOR TO JANUARY 20, 2025, WERE FUNDED UNDER PREVIOUS ADMINISTRATIONS AND MAY NOT REFLECT THE PRIORITIES AND POLICIES OF THE CURRENT ADMINISTRATION.** MASTITIS IS A HIGHLY PREVALENT DISEASE IN THE DAIRY INDUSTRY AND THE MAIN REASON FOR THE USE OF ANTIBIOTICS IN US DAIRY FARMS. THERE IS INCREASING PRESSURE ON THE INDUSTRY TO REDUCE ANTIBIOTIC USAGE, AND IMMUNOTHERAPEUTICS HAVE EMERGED AS AN ALTERNATIVE TO ANTIBIOTICS FOR THE PREVENTION AND CONTROL OF MASTITIS. IN OUR PRELIMINARY STUDIES, AN IMMUNOTHERAPEUTIC COMPOUND, MUCOSIMMUNE, HAS BEEN SHOWN TO UPREGULATE THE INNATE IMMUNE RESPONSE IN THE MAMMARY GLAND OF CATTLE. THUS, THE OVERALL OBJECTIVE OF OUR MULTI-DISCIPLINARY TEAM (I.E., DAIRY HEALTH AND MANAGEMENT, IMMUNOLOGY, MICROBIOMICS, AND BIOINFORMATICS) IS TO INVESTIGATE THE IMMUNE ACTIVATION DURING THE PERIPARTURIENT PERIOD TO IMPROVE MAMMARY GLAND IMMUNE RESPONSE AND DECREASE THE INCIDENCE OF MASTITIS WITHOUT THE USE OF ANTIBIOTICS. IN THIS STUDY WE WILL APPROACH OUR LONG-TERM GOAL BY DETERMINING THE EFFECT OF MUCOSIMMUNE ON (1) THE INNATE IMMUNE RESPONSE IN THE MAMMARY GLAND DURING THE PERIOD IMMEDIATELY BEFORE AND AFTER PARTURITION, AND (2) THE RESISTANCE TO BACTERIAL INFECTION OF THE MAMMARY GLAND. THESE COMPLEMENTARY STUDIES WILL IMPROVE OUR KNOWLEDGE OF HOW OUR MUCOSIMMUNE MAY AFFECT THE INNATE IMMUNE RESPONSE IN THE MAMMARY GLAND AND WHETHER SUCH AN APPROACH CAN BE EFFECTIVE IN IMPROVING MAMMARY GLAND RESISTANCE TO INTRAMAMMARY INFECTIONS. THE KNOWLEDGE GENERATED BY THESE STUDIES WILL BE ESSENTIAL FOR THE LATER DESIGN OF RANDOMIZED CLINICAL TRIALS IN THE FIELD. OUR ULTIMATE LONG-TERM GOAL WITH THIS RESEARCH IS TO DEVELOP EFFECTIVE IMMUNE-BASED SOLUTIONS FOR IMPROVING UDDER HEALTH AS ALTERNATIVES TO ANTIBIOTIC THERAPY.