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

Abstract

Vaccines may improve the control and eradication of bovinetuberculosis. However, the evaluation of experimental candidates requires the assessment of theprotection, excretion, transmission and biosafety. A natural transmission trial among likely infectedanimals was conducted. Methods: Seventy-four male heifers were randomly distributed (five groups)and vaccinated subcutaneously with attenuated strains (M. bovis ∆mce2 or M. bovis ∆mce2-phoP), arecombinant M. bovis BCG Pasteur (BCGr) or M. bovis BCG Pasteur. Then, they cohoused with anaturally infected bTB cohort under field conditions exposed to the infection. Results: A 23% oftransmission of wild-type strains was confirmed (non-vaccinated group). Strikingly, first vaccinationdid not induce immune response (caudal fold test and IFN-gamma release assay). However, after74 days of exposure to bTB, animals were re-vaccinated. Although their sensitization increasedthroughout the trial, the vaccines did not confer significant protection, when compared to the nonvaccinated 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 nonvaccinated group (p > 0.076). Respiratory and digestive excretion of viable vaccine candidateswas undetectable. To note, the group vaccinated with M. bovis ∆mce2-phoP exhibited the highestproportion of animals without macroscopic lesions, compared to the one vaccinated with BCG,although this was not statistically supported. Conclusions: This highlights that further evaluationof these vaccines would not guarantee better protection. The limitations detected during the trialare discussed regarding the transmission rate of M. bovis wild-type, the imperfect test for studyingsensitization, the need for a DIVA diagnosis and management conditions of the trials performedunder routine husbandry conditions. Re-vaccination of likely infected bovines did not highlight aconclusive result, even suggesting a detrimental effect on those vaccinated with M. bovis BCG.