We evaluated whether immune responses stimulated by Salmonella vaccine carriers can be modulated by using different promoters to drive antigen expression. Mice were orally immunized with strains transfected with plasmids carrying β-galactosidase (β-gal) under the control of either a constitutive or an in vivo-activated promoter. While β-gal-reactive IgG1, IgG2a, IgG2b and IgG3 were detected in sera of mice immunized with Salmonella expressing constitutively β-gal, higher titers dominated by IgG2a and IgG2b were detected in sera when the in vivo-activated promoter was used. β-gal-specific proliferative responses of spleen-derived CD4+ T lymphocytes were similar in both groups. However, CD4+ T lymphocytes from mice immunized with the constitutive promoter secreted IL-4, IL-5, IL-6, IL-10 and IFN-γ (Th1/Th2 pattern), whereas CD4+ cells mainly secreted IFN-γ (Th1 pattern) when the second construct was used. The spleens of all immunized mice contained β-gal-reactive CD8+ CTL precursors. The vaccine prototypes were tested for their capacity to control seeding and/or development within the lung of an intravenously delivered aggressive fibrosarcoma transfected with β-gal. Reduced metastasis and significantly increased mean survival times were observed in all vaccinated mice. However, protection was improved when the carrier expressed β-gal upon infection (80% versus 50% survival, p <0.05).
|Number of pages||10|
|Journal||European Journal of Immunology|
|Publication status||Published - 2000|
- In vivo activated promoter
- Salmonella aroA
ASJC Scopus subject areas