DEVELOPING EFFECTIVEANTIMICROBIAL-ALTERNATIVE STRATEGIES TO CONTROL LIVESTOCK DISEASES ARE NATIONAL PRIORITIES AND VITAL TO PROTECTING FOOD SECURITY. OUR LONG-TERM GOAL IS TO PROMOTE SUSTAINABLE AND PROFITABLE LIVESTOCK PRODUCTION BY DEVELOPING A CONTEMPORARY BOVINE ANAPLASMOSIS VACCINE THAT IS COST-EFFECTIVE, SAFE, AND CAPABLE OF INDUCING LONG-LASTING BROAD PROTECTION AGAINST CLINICAL ANAPLASMOSIS, AN ENDEMIC TICK-BORNE BACTERIAL DISEASE THAT IS CONSERVATIVELY ESTIMATED TO COST THE U.S. CATTLE INDUSTRY $300 MILLION PER YEAR. TETRACYCLINE ANTIMICROBIALS ARE THE ONLY FDA-APPROVED DRUG TO TREAT ANAPLASMOSIS AND ARE COMMONLY ADMINISTERED DURING THE ENTIRE PASTURE SEASON. CONTINUOUS PROLONGED EXPOSURE TO A SINGLE DRUG-CLASS IS NOT A JUDICIOUS USE OF MEDICALLY-IMPORTANT ANTIMICROBIALS AND PROMOTES DEVELOPMENT OF ANTIMICROBIAL RESISTANCE. WE HYPOTHESIZE THAT DEVELOPING AN ANAPLASMOSIS VACCINE BASED ON REGIONALLY-REPRESENTATIVE ANAPLASMA MARGINALE(THE AGENT OF BOVINE ANAPLASMOSIS) ANTIGEN COMBINED WITH MODERN ADJUVANTS WILL PROVIDE BROAD PROTECTION AGAINST CLINICAL DISEASE IN VACCINATED CATTLE. THROUGH COOPERATION BETWEEN SCIENTISTS, IMMUNOLOGISTS, CLINICIANS, AND EPIDEMIOLOGISTS, WE WILL TEST THIS HYPOTHESIS BY: I) EVALUATINGA. MARGINALESTRAIN DIVERSITY; II) EVALUATING THE EFFICACY OF THE PROTOTYPE ANAPLASMOSIS VACCINE TO PROVIDE BROAD PROTECTION UPON INFECTION OF CATTLE WITH DIFFERENT STRAINS OFA. MARGINALE; AND, III) EVALUATING THE EFFICACY OF THE PROTOTYPE ANAPLASMOSIS VACCINE DELIVERED IN A SLOW-RELEASE IMPLANT (SINGLE IMMUNIZATION) VERSUS A TRADITIONAL NEEDLE IMMUNIZATION SERIES (MULTIPLE IMMUNIZATIONS). AS FURTHER PROOF-OF-CONCEPT, WE WILL TEST OUR VACCINE DESIGN CONCEPT IN TANZANIA, ANOTHER LARGE CATTLE-PRODUCTION COUNTRY ENDEMIC FOR ANAPLASMOSIS, WITH FIELD-CHALLENGED CATTLE UNDER NATURAL HIGH-STRESS CONDITIONS. SUCCESSFUL COMPLETION OF THIS PROPOSAL WILL DELIVER A PROTOTYPE BROADLY EFFICACIOUS ANAPLASMOSIS VACCINE.AN EFFICACIOUS BOVINE ANAPLASMOSIS VACCINE WILL: I) REDUCE ECONOMIC LOSSES ASSOCIATED WITH CLINICAL DISEASE, II) REDUCE EXPENSES RELATED TO FEEDING ANTIMICROBIAL-MEDICATED FEED PRODUCTS FOR EXTENDED TIME PERIODS, AND III) PROTECT THE THERAPEUTIC EFFICACY OF MEDICALLY-IMPORTANT ANTIMICROBIALS FOR FOOD SAFETY AND PUBLIC HEALTH.