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

Abstract

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‐γ 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‐γ production in splenic lymphocytes than nBCG. This impaired induction of IFN‐γ 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.