**AWARDS ISSUED PRIOR TO JANUARY 20, 2025, WERE FUNDED UNDER PREVIOUS ADMINISTRATIONS AND MAY NOT REFLECT THE PRIORITIES AND POLICIES OF THE CURRENT ADMINISTRATION.** BABESIA IS A TICK BORNE DISEASE WITH HIGH IMPACT IN CATTLE INDUSTRIES WORLDWIDE. THE DISEASE WAS ERADICATED FROM THE US BY ELIMINATING THE TICK VECTOR. THE RECENT INCREASED RISK FOR THE RE-EMERGENCE OF BOVINE BABESIOSIS IN THE US THROUGH THE US-MEXICO BORDER INDICATES THAT BABESIA BOVIS CONTINUES TO BE A SIGNIFICANT THREAT TO US CATTLE INDUSTRY. LIVE ATTENUATED VACCINES AGAINST B. BOVIS ARE AVAILABLE, BUT NOT PERMITTED IN THE US DUE TO THEIR SEVERAL LIMITATIONS. THEREFORE, DEVELOPMENT OF EFFICIENT, NEW GENERATION VACCINES TO CONTROL B. BOVIS IS A HIGH PRIORITY. IN THE PRESENT PROJECT WE PROPOSE TO DEVELOP A SUBUNIT VACCINE TO PROTECT CATTLE AGAINST CLINICAL SIGNS OF ACUTE BOVINE BABESIOSIS USING A PREVIOUSLY UNTESTED APPROACH BASED ON IMMUNOSUBDOMINANT ANTIGENS. WE SELECTED TOTARGET SUCHSUBDOMINANT ANTIGENS, THOSETHAT INDUCE POOR OR IMMUNE SUPPRESSED RESPONSES DURING NATURAL INFECTIONS, BECAUSE THEY MAY BE MORE LIKELYESSENTIAL FOR PARASITE SURVIVAL. WE PLAN TO GENERATE AND TEST A VACCINE INCLUDING TWO PREVIOUSLY CHARACTERIZED ANTIGENICALLY SUBDOMINANT ANTIGENS OF KNOWN FUNCTIONAL RELEVANCE. THE NOVEL SUBUNIT VACCINE WILL BE TESTED IN CATTLE TRIALS.WE EXPECT THAT THE VACCINATED ANIMALS WILL CONTROL PARASITEMIA, SHOW MILD SIGNS OF INFECTION, AND SURVIVE CHALLENGE WITH A VIRULENT STRAIN OF B. BOVIS. WE PREDICT THAT THE NOVEL SUBUNIT VACCINE WILL PRIME THE IMMUNE SYSTEMS OF CATTLE, SLOWDOWN PARASITEMIA, AND ULTIMATELY PROVIDE TIME FOR THE HOST TO MOUNT A PROTECTIVE ADAPTIVE IMMUNE RESPONSE TARGETED TO CONTROL ACUTE DISEASE. CONSIDERING OUR GOAL TO DEVELOP A SUBUNIT VACCINE TO CONTROL ACUTE BOVINE BABESIOSIS, THIS PROPOSAL WILL TAKE A STEP FORWARD BOTH THE NIFA MISSION AND THE AFRI STRATEGIC GOAL TO PROVIDE AMERICANS ACCESS TO SAFE, NUTRITIOUS, AND SECURE FOOD SUPPLY.