Longitudinal Pathogenesis Study of Young Red Deer (Cervus elaphus) after Experimental Challenge with Mycobacterium avium subsp. paratuberculosis (MAP).

Paratuberculosis progresses more quickly in young red deer than in sheep or cattle. This study describes the clinical, immunological and pathological changes over a 50-week period in fourteen 4-month-old red deer that received heavy oral challenge with Mycobacterium avium subsp. paratuberculosis (MAP). At 4 and 12 weeks post challenge they were anaesthetized and a section of jejunal lymph node was surgically removed for culture, histopathology, and genetic studies. All 14 deer became infected, none were clinically affected, and they had varying degrees of subclinical disease when killed at week 50. Week 4 biopsies showed no paratuberculosis lesions, but MAP was cultured from all animals. At weeks 12 and 50 histopathological lesions ranged from mild to severe with corresponding low-to-high antibody titres, which peaked at 12-24 weeks. IFN-γ responses peaked at 8-15 weeks and were higher in mildly affected animals than in those with severe lesions.

Manipulation of immune responses to Mycobacterium bovis by vaccination with IL-2- and IL-18-secreting recombinant bacillus Calmette Guerin.

Bacillus Calmette Guerin (BCG) has been reported to show variable efficacy as a vaccine against tuberculosis. We demonstrated that the secretion of biologically active IL-2 (rBCG/IL-2),but not IL-18 (rBCG/IL-18), by BCG improves its ability to induce and maintain a strong type 1 immune response in BALB/c mice. rBCG/IL-2 induced significantly higher Ag-specific proliferative responses, high IFN-gamma production and serum titres of IgG2a 16 weeks after vaccination. This immune profile was correlated to an increased rate of clearance of non-pathogenic mycobacteria (live BCG delivered intranasally). Surprisingly, however,this strong type 1 immune profile induced no greater protective immunity against aerosol challenge with virulent Mycobacterium bovis than that induced by normal BCG (nBCG). By comparison,vaccination with rBCG/IL-18 was found to induce significantly less IFN-gamma production in splenic lymphocytes than nBCG. This impaired induction of IFN-gamma was correlated to a significantly lower protective efficacy against M. bovis challenge, as compared to nBCG. The data suggest that manipulation of the immune response to tuberculosis and tuberculosis vaccines will require a more complete understanding of the factors that are important in generating a protective immune response.