IL‐2‐secreting recombinant bacillus Calmette Guerin can overcome a Type 2 immune response and corticosteroid‐induced immunosuppression to elicit a Type 1 immune response

The efficacy of bacillus Calmette Guerin (BCG) as a vaccine against tuberculosis is adversely affected by both genetic and environmental factors on the immune system. In this study we have demonstrated that a recombinant BCG (rBCG) secreting biologically active IL‐2 has the ability to induce a Th1 profile in both immunocompromised and in IL‐4 transgenic (Tg) mice. Dexamethasone (DXM) was administered orally to mice prior to vaccination with either rBCG or normal BCG (nBCG). Six weeks post‐vaccination with rBCG, splenocytes from DXM‐treated mice exhibited a strong antigen‐specific proliferative response, while also secreting large amounts of IFN‐γ and low levels of IgG1. The opposite profile occurred when DXM‐treated mice were vaccinated with nBCG. Splenocytes from these mice showed no significant proliferation and produced a cytokine profile associated with a Th2 immune response, in addition to exhibiting high levels of serum IgG1. In the IL‐4 Tg model, mice vaccinated with rBCG again produced a strong Th1 immune response, exhibiting a high antigen‐specific IFN‐γ:IL‐4 ratio and a concomitantly high IgG2a:IgG1 ratio. IL‐4 Tg mice vaccinated with nBCG produced the opposite profile. These findings suggest that BCG can be made more robust by incorporating immunopotentiating cytokines into the vaccine.