Vaccination is a tool that could be beneficial in managing the high prevalence of brucellosis in free-ranging bison in Yellowstone National Park. In this study, we characterized immunologic responses and protection against experimental challenge after vaccination of bison with Brucella abortus strain RB51 (RB51) or a recombinant RB51 strain overexpressing superoxide dismutase (sodC) and glycosyltransferase (wboA) genes (RB51؉sodC,wboA). Bison were vaccinated with saline only or with 4.6 ؋ 10 10 CFU of RB51 or 7.4 ؋ 10 10 CFU of RB51؉sodC,wboA (n ؍ eight animals/treatment). Bison vaccinated with RB51 or RB51؉sodC,wboA had greater (P < 0.05) antibody responses, proliferative responses, and production of gamma interferon to RB51 after vaccination than did nonvaccinates. However, bison vaccinated with RB51؉sodC,wboA cleared the vaccine strain from draining lymph nodes faster than bison vaccinated with the parental RB51 strain. Immunologic responses of bison vaccinated with RB51؉sodC,wboA were similar to responses of bison vaccinated with RB51. Pregnant bison were intraconjunctivally challenged in midgestation with 10 7 CFU of B. abortus strain 2308. Bison vaccinated with RB51, but not RB51؉sodC,wboA vaccinates, had greater protection from abortion, fetal/uterine, mammary, or maternal infection than nonvaccinates. Our data suggest that the RB51؉sodC,wboA strain is less efficacious as a calfhood vaccine for bison than the parental RB51 strain. Our data also suggest that the RB51 vaccine is a currently available management tool that could be utilized to help reduce brucellosis in free-ranging bison.