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International Immunology, Vol. 14, No. 7, pp. 793-800, July 2002
© 2002 Japanese Society for Immunology

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

Sarah L. Young1, Michael A. O’Donnell2 and Glenn S. Buchan1

1 Department of Microbiology, University of Otago, 700 Cumberland Street, PO Box 56, Dunedin, New Zealand 2 Department of Urology, Iowa University, Iowa City, IA 52242, USA

Correspondence to: G. Buchan; E-mail: glen.buchan{at}stonebow.otago.ac.nz
Transmitting editor: K. Shortman

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-{gamma} 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-{gamma}: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.

Keywords: bacillus Calmette Guerin, cytokine, immunotherapy, Th1/Th2, tuberculosis, vaccination


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