Caprine livestock are significant reservoirs of the complex (MTBC), contributing to tuberculosis (TB) transmission among animals and humans. The P22 protein immunocomplex (P22PI), derived from bovine tuberculin, shows immunostimulating capacity and is used for TB diagnosis. This study assessed the immunogenicity and protective efficacy of P22PI in two groups of goats: 24 naïve goats (12 immunised, 12 controls) from a TB-free herd, and 24 infected goats (12 immunised, 12 controls), referred to as pre-infected animals, from a -infected herd. Both were exposed for 5 months to -naturally infected goats. Reactors to single and comparative intradermal tuberculin (SIT and SCIT, respectively) tests and interferon-gamma release assay (IGRA) significantly increased ( < 0.05) in both groups 5 months' post-exposure, with no significant differences between immunised and control animals. However, immunised animals exhibited a significantly higher ( < 0.05) antibody response against P22PI. Most naïve animals (83.3%) and all pre-infected animals developed TB-compatible lesions, with extensive necrosis in the lungs and associated lymph nodes, compared to 50% and 83.3% of control animals, respectively. These findings suggest that while P22PI stimulates an intense antibody response under the conditions of the present study, it does not confer protection against TB and may exacerbate disease severity.