** AWARDS ISSUED PRIOR TO JANUARY 20, 2025, WERE FUNDED UNDER PREVIOUS ADMINISTRATIONS AND MAY NOT REFLECT THE PRIORITIES AND POLICIES OF THE CURRENT ADMINISTRATION.** OVINE TUBERCULOSIS (BTB), CAUSED BY MYCOBACTERIUM TUBERCULOSIS VARIANT BOVIS (MBO), IS ONE OF THE MOST DAMAGING DISEASES IN AGRICULTURE WORLDWIDE. THE RISE IN BTB INFECTED DEER AND CATTLE HERDS IN MICHIGAN, HAS LED TO A STATE OF URGENCY DUE TO ASSOCIATED ANIMAL TRADE AND MOVEMENT RESTRICTIONS. CONTROLLING THE DISEASE IN ANIMALS IS A PRIMARY APPROACH TO PREVENTING/MITIGATING SPREAD OF MBO INTO AND FROM WILDLIFE OR HUMAN POPULATIONS. THIS STUDY PROPOSES A NOVEL VACCINE DESIGN AROUND A CENTRAL PARADIGM OF MICROBIAL PATHOGENESIS THAT POSITS THAT IMMUNE RESPONSES AGAINST VIRULENCE FACTORS OF M. BOVIS ARE SUFFICIENT AND EFFECTIVE TO PROTECT ANIMALS AGAINST MBO INFECTION. THESE HIGHLY CONSERVED IMMUNOGENIC PEPTIDES/PROTEINS FROM M. TUBERCULOSIS COMPLEX WILL BE GENETICALLY ENGINEERED INTO THE UBIQUITOUS SOIL BACTERIUM (AND A PROBIOTIC), BACILLUS SUBTILIS, TO BE EXPRESSED AND DISPLAYED ON ITS SPORES. RECOMBINANT SPORES ARE HEAT- STABLE, EASILY STORED, AND EASILY ADMINISTERED MUCOSAL (ORAL OR INTRANASAL) VACCINE. RECOMBINANT SPORES WILL BE TESTED, IN THIS STUDY, FOR THEIR ABILITY TO ELICIT ANTI-MBO CELLULAR AND HUMORAL IMMUNE RESPONSES AND IN-VIVO TESTED FOR BACTERIAL KILLING USING IN A ORAL VACCINATION-CHALLENGE STUDY DESIGN.