** AWARDS ISSUED PRIOR TO JANUARY 20, 2025, WERE FUNDED UNDER PREVIOUS ADMINISTRATIONS AND MAY NOT REFLECT THE PRIORITIES AND POLICIES OF THE CURRENT ADMINISTRATION.** BOVINE TUBERCULOSIS (BTB) CAUSED BYMYCOBACTERIUM TUBERCULOSISVARIANTBOVIS(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 OFM. BOVISARE SUFFICIENT AND EFFECTIVE TO PROTECT ANIMALS AGAINST MBO INFECTION. THESE HIGHLY CONSERVED IMMUNOGENIC PEPTIDES/PROTEINS FROMM. TUBERCULOSISCOMPLEX 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 AN ORAL VACCINATION-CHALLENGE STUDY DESIGN.