Differences in local immune response of bait Mycobacterium bovis heat-inactivated vaccinated badgers showing exacerbated tuberculous lesions after challenge

European badgers (Meles meles) are reservoirs for animal tuberculosis (TB) in some European countries, complicating TB control in cattle. Badger vaccination and a deeper understanding of the subsequent protection mechanisms are necessary for effective TB control. In a previous study, two of eight badgers immunized with the heat-inactivated Mycobacterium bovis (HIMB) vaccine exhibited an unusual immune response (divergent), developing exacerbated lesions. The present study aimed to describe the local immune response in divergent badgers (those with severe disease progression), with respect to that observed in standard (where the vaccine showed efficacy) and control badgers. Immunohistochemistry was performed to evaluate immune cells (macrophages, T and B lymphocytes, plasma cells), and proteins (TGF-β, IL-10, Fox-P3) within TB granulomas in the lung and bronchial lymph node (LN), after TB challenge. Lung lesion volume, bacterial load and immunological response were also evaluated. The divergent immune response was characterized by elevated IL-10 and Fox-P3, few macrophages and high B lymphocytes (mainly in lungs), suggesting a Th1/Th2 imbalance with reduced Th1 cellular immunity leading to severe TB. In contrast, vaccinated badgers with a standard immune response showed a balanced response, with significantly lower bacterial loads (85.5% LN and 99.9% lung) than control group. This study provides new insights into the immune mechanisms in HIMB-vaccinated badgers, to improve TB control strategies.