** AWARDS ISSUED PRIOR TO JANUARY 20, 2025, WERE FUNDED UNDER PREVIOUS ADMINISTRATIONS AND MAY NOT REFLECT THE PRIORITIES AND POLICIES OF THE CURRENT ADMINISTRATION.** OUR GOAL IS TO REDUCE THE BURDEN OF INFECTIOUS DISEASE IN LIVESTOCK. WE WILL TEST A PARADIGM OF NUTRITIONAL PROGRAMMING OF THE IMMUNE SYSTEM FOR LIFELONG RESILEINCY. NEARLY 20% OF DAIRY HEIFERS BORN IN THE U.S DO NOT MAKE IT TO THEIR FIRST LACTATION. MORTALITY AND MORBIDITY IN EARLY LIFE ARE THE BIGGEST FACTORS FOR FAILURE OF DAIRY REPLACEMENT HEIFERS FOLLOWED BY POOR GROWTH AND REPRODUCTIVE SUCCESS IN LATER LIFE. AT ESTIMATED COSTS OF $1,500 TO $2,000 TO RAISE REPLACEMENT HEIFERS, THIS IS A MAJOR ECONOMIC BURDEN FOR DAIRY FARMS. SIMILAR INEFFICIENCIES OCCUR ACROSS ALL SECTORS OF ANIMAL AGRICULTURE; THUS, PROGRAMMING THE FETUS FOR LIFELONG SUCCESS HAVE MASSIVE ECONOMIC IMPLICATIONS FOR AGRICULTURE AND ALLIED INDUSTRIES. THIS PROJECT BUILDS ON OUR ONGOING RESEARCH SHOWING MULTIPLE POSITIVE BENEFITS OF VITAMIN D IN HEALTH AND IMMUNITY OF LIVESTOCK. EMERGING RESEARCH ALSO ILLUSTRATES THAT THE PROTECTIVE EFFECTS OF VITAMIN D GO BEYOND ITS IMMEDIATE ROLE AT THE TIME OF DISEASE INSULT, BUT VIA ITS ABILITY TO AFFECT LONG-TERM PRODUCTIVITY (A.K.A., PROGRAMMING), IT CAN ACTUALLY INFLUENCE THE PHENOTYPIC STATUS OF DEVELOPING IMMUNE CELLS. THE CENTRAL HYPOTHESIS OF THIS PROPOSAL IS THAT MATERNAL AND NEONATAL VITAMIN D SUPPLEMENTATION PROGRAMS THE IMMUNE SYSTEM FOR IMPROVED LIFETIME HEALTH AND PRODUCTIVITY. OUR EXPERIMENTAL OBJECTIES ARE TO 1) DETERMINE THE EFFECTS OF MATERNAL AND NEONATAL VITAMIN D ON PROGRAMMING OF IMMUNITY IN CALVES BY ASSESSMENT OF STANDARD IMMUNE ASSAYS AND NOVEL GENOMIC APPROACHES, AND 2) DETERMINE EFFECTS OF MATERNAL AND NEONATAL VITAMIN D ON HEALTH AND PERFORMANCE OF CALVES BY ASSESSMENT OF DISEAE INCICENCE AND SEVERITY, AND GROWTH AND PRODUCTIVITY OF CALVES. THE OUTCOMES ARE EXPECTED TO TRANSFORM SCIENTIFIC PARADIGMS RESULTING IN NEW RESEARCH QUESTIONS AND WAYS WE APPROACH RESEARCH. THE OUTCOMES ALSO ARE EXPECTED TO BE IMMEDIATELY APPLICABLE TO AGRIGULTURAL PRODUCERS AND PRACTITIONERS BY INFORMING BEST PRACTICES FOR NUTRITION, MANAGEMENT AND VETERINARY TREATMENT OF ANIMALS.