Field Trial with Vaccine Candidates Against Bovine Tuberculosis Among Likely Infected Cattle in a Natural Transmission Setting

<b>Background/Objectives</b>: Vaccines may improve the control and eradication of bovine tuberculosis. However, the evaluation of experimental candidates requires the assessment of the protection, excretion, transmission and biosafety. A natural transmission trial among likely infected animals was conducted. <b>Methods</b>: Seventy-four male heifers were randomly distributed (five groups) and vaccinated subcutaneously with attenuated strains (<i>M. bovis Δmce2</i> or <i>M. bovis Δmce2</i>-<i>phoP</i>), a recombinant <i>M. bovis</i> BCG Pasteur (BCGr) or <i>M. bovis</i> BCG Pasteur. Then, they cohoused with a naturally infected bTB cohort under field conditions exposed to the infection. <b>Results</b>: A 23% of transmission of wild-type strains was confirmed (non-vaccinated group). Strikingly, first vaccination did not induce immune response (caudal fold test and IFN-gamma release assay). However, after 74 days of exposure to bTB, animals were re-vaccinated. Although their sensitization increased throughout the trial, the vaccines did not confer significant protection, when compared to the non-vaccinated group, as demonstrated by pathology progression of lesions and confirmatory tools. Besides, the likelihood of acquiring the infection was similar in all groups compared to the non-vaccinated group (<i>p</i> > 0.076). Respiratory and digestive excretion of viable vaccine candidates was undetectable. To note, the group vaccinated with <i>M. bovis Δmce2-phoP</i> exhibited the highest proportion of animals without macroscopic lesions, compared to the one vaccinated with BCG, although this was not statistically supported. <b>Conclusions</b>: This highlights that further evaluation of these vaccines would not guarantee better protection. The limitations detected during the trial are discussed regarding the transmission rate of <i>M. bovis</i> wild-type, the imperfect test for studying sensitization, the need for a DIVA diagnosis and management conditions of the trials performed under routine husbandry conditions. Re-vaccination of likely infected bovines did not highlight a conclusive result, even suggesting a detrimental effect on those vaccinated with <i>M. bovis</i> BCG.