THE 2014 NATIONAL ANIMAL HEALTH MONITORING SYSTEM (NAHMS) FOR U.S. DAIRIES REPORTED THAT 56.4% OF PRE-WEANED CALF MORTALITY WAS DUE TO DIARRHEA. THE PARASITE CRYPTOSPORIDIUM IS THE MAIN CAUSE OF DIARRHEA IN NEONATAL CALVES GLOBALLY. THERE ARE NO VACCINES TO PREVENT CRYPTOSPORIDIOSIS IN LIVESTOCK, AND AVAILABLE THERAPEUTIC DRUGS HAVE LIMITED OR NO EFFICACY. THUS, THERE IS A PRESSING NEED FOR POTENT ANTI-CRYPTOSPORIDIAL THERAPEUTICS.VACCINE DEVELOPMENT IS HAMPERED WITH MANY CHALLENGES INCLUDING, UNTIL RECENTLY, THE LACK OF TOOLS TO GENETICALLY MODIFY CRYPTOSPORIDIUM AND LIMITED KNOWLEDGE OF THE MOLECULAR IDENTITIES OF VIABLE VACCINE TARGETS. VACCINES MAY OFFER PROTECTION TO MORE MATURE CALVES BUT ARE INEFFECTIVE AT PREVENTING NEONATAL CRYPTOSPORIDIOSIS BECAUSE INFECTION OFTEN OCCURS WITHIN THE FIRST WEEK OF LIFE, NEWBORN CALVES HAVE AN IMMATURE MUCOSAL IMMUNE SYSTEM, AND THERE IS ALSO INSUFFICIENT TIME TO MOUNT PROTECTIVE IMMUNE RESPONSES GIVEN THE TIMING OF INFECTION. THE MORE VIABLE STRATEGIES TO PREVENT CRYPTOSPORIDIUM-INDUCED DEATH OF NEONATAL CALVES ARE TO (1) PREVENT INFECTION BY THE PARASITE OR (2) TREAT AND MANAGE AN ONGOING INFECTION.THE ULTIMATE GOAL OF THIS RESEARCH PROJECT IS TO GENERATE NOVEL, SAFE, TARGETED AND COST-EFFECTIVE THERAPEUTICS FOR MITIGATING CRYPTOSPORIDIUM INFECTION. PROBIOTIC SYNTHETIC LACTIC ACID BACTERIA (SYNLAB) STRAINS WILL BE ENGINEERED TO EXPRESS CANDIDATE CRYPTOSPORIDIUM MOLECULES. THESE NOVEL SYNLAB STRAINS MAY BE USED TO PREVENT BOVINE CRYPTOSPORIDIOSIS VIA TWO APPLICATIONS: (1) BY COMPETING FOR AND BLOCKING THE ATTACHMENT OF THE PARASITE TO THE INTESTINES OF NEONATAL CALVES, AND (2) BY PROVIDING PASSIVE IMMUNITY TO NEONATAL CALVES THROUGH THE CONSUMPTION OF MATERNAL COLOSTRUM DERIVED FROM SYNLAB-TREATED COWS. THIS RESEARCH PROJECT, THEREFORE, ADDRESSES KEY PROBLEMS RELATED TO ANIMAL HEALTH AND PRODUCTION AND ANIMAL PRODUCTS, A PRIMARY AFRI FARM BILL PRIORITY AREA.