title: 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.
abstract: 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 T(h)1 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 T(h)2 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 T(h)1 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.
authors.affiliation: Department of Microbiology, University of Otago, 700 Cumberland Street, PO Box 56, Dunedin, New Zealand.
authors.forename: Sarah L
authors.initials: SL
authors.lastname: Young
authors.forename: Michael A
authors.initials: MA
authors.lastname: O'Donnell
authors.forename: Glenn S
authors.initials: GS
authors.lastname: Buchan
mesh_terms: D000818:Animals; D001500:BCG Vaccine / Q000008:administration & dosage / Q000276:immunology*; D003907:Dexamethasone; D005938:Glucocorticoids; D007111:Immunity, Cellular; D016867:Immunocompromised Host / Q000276:immunology*; D007074:Immunoglobulin G / Q000097:blood; D007371:Interferon-gamma / Q000096:biosynthesis; D007376:Interleukin-2 / Q000096:biosynthesis*; D015847:Interleukin-4 / Q000235:genetics; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D018417:Th1 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*; D014611:Vaccination; D014614:Vaccines, Synthetic / Q000276:immunology
chemical_list: D001500:BCG Vaccine; D005938:Glucocorticoids; D007074:Immunoglobulin G; D007376:Interleukin-2; D014614:Vaccines, Synthetic; D015847:Interleukin-4; D003907:Dexamethasone; D007371:Interferon-gamma