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.
Young
Sarah
S
Department of Microbiology,University of Otago, Dunedin, New Zealand.
O'Donnell
Michael
M
Lockhart
Euan
E
Buddle
Bryce
B
Slobbe
Lynn
L
Luo
Yi
Y
De Lisle
Geoff
G
Buchan
Glenn
G
D000818:Animals; D001500:BCG Vaccine / Q000145:classification / Q000235:genetics* / Q000276:immunology*; D002417:Cattle; D002478:Cells, Cultured; D004274:DNA, Recombinant / Q000276:immunology; D007132:Immunoglobulin Isotypes / Q000032:analysis; D007371:Interferon-gamma / Q000032:analysis; D020382:Interleukin-18 / Q000096:biosynthesis / Q000235:genetics*; D007376:Interleukin-2 / Q000096:biosynthesis / Q000235:genetics*; D051379:Mice; D008807:Mice, Inbred BALB C; D009163:Mycobacterium bovis / Q000276:immunology* / Q000472:pathogenicity; D013154:Spleen / Q000276:immunology / Q000382:microbiology; D013997:Time Factors; D014611:Vaccination; D019444:Vaccines, DNA / Q000276:immunology; D014774:Virulence
D001500:BCG Vaccine; D004274:DNA, Recombinant; D007132:Immunoglobulin Isotypes; D020382:Interleukin-18; D007376:Interleukin-2; D019444:Vaccines, DNA; D007371:Interferon-gamma