INFECTION WITH MYCOBACTERIUM AVIUM SUBSPECIES PARATUBERCULOSIS (M. AP) CAUSES SEVERE ECONOMIC LOSSES TO THE DAIRY INDUSTRY IN THE USA AND WORLDWIDE. IN THE USA ALONE, EVERY DAIRY HERD LOSES $400/COW ON AVERAGE DUE TO COMPLICATIONS FROM JOHNE'S DISEASE (JD). WITH THE SUPPORT FROM THE USDA/NIFA PROGRAM, WE WERE ABLE TO DEVELOP HIGHLY PROTECTIVE VACCINE CANDIDATES AGAINST JOHNE'S DISEASE THAT REQUIRE FURTHER DEVELOPMENT BEFORE USE IN NATIONAL CONTROL PROGRAMS. FOR EXAMPLE, LITTLE INFORMATION IS CURRENTLY AVAILABLE ABOUT THE PERFORMANCE OF THE LIVE VACCINE CANDIDATES (LAV) IN THE TARGET HOST, CATTLE. EVEN WHEN AN EFFECTIVE VACCINE IS DEVELOPED, WE STILL DON'T HAVE A STRATEGY OF HOW TO EMPLOY SUCH VACCINE FOR A SUCCESSFUL CONTROL PROGRAM UNDER FIELD CONDITIONS. THE ULTIMATE GOAL OF THIS PROJECT IS TO UNDERSTAND THE DYNAMICS OF THE DEVELOPMENT OF JD PROTECTIVE IMMUNITY FOLLOWING LAV IMMUNIZATION, TO HELP IN DEVELOPING AN EFFECTIVE CONTROL STRATEGY AGAINST JD. TO ACHIEVE OUR GOALWE WILL ANALYZE THE PERSISTENCE AND IMMUNITY OF LIVE VACCINE CANDIDATES (LAV) IN CALVES, THE TARGET HOST FOR JD VACCINE DEVELOPMENT. WE WILL ALSO EXAMINE HOW LAV GENERATE AN EFFECTIVE IMMUNE RESPONSES THAT CAN OVERCOME JD. FINALLY, WE WILL CHARACTERIZE HOW CALVES RESPONSE TO M. AP INFECTION AND VACCINATION. OVERALL, THE OUTCOMES OF THE PROPOSED AIMS WILL ALLOW US TO HAVE A BETTER UNDERSTANDING OF JD DISEASE PROGRESSION AND COULD IDENTIFY KEY MARKERS USED FOR THE DIAGNOSIS OF JD. MORE IMPORTANTLY, OUR STUDY COULD ESTABLISH AN OPTIMUM PROTOCOL FOR EFFECTIVE IMMUNIZATION, DESPERATELY NEEDED TO CONTROL JD WHICH WILL IN SUPPORT WITH THE MISSION OF THE ANIMAL HEALTH AND DISEASE PROGRAM AT THE NIFA/AFRI.