Modulation of host immune responses stimulated by Salmonella vaccine carrier strains by using different promoters to drive the expression of the recombinant antigen

Eva Medina, Paola Paglia, Manfred Rohde, Mario P. Colombo, Carlos Alberto Guzmán

Research output: Contribution to journalArticle

Abstract

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).

Original languageEnglish
Pages (from-to)768-777
Number of pages10
JournalEuropean Journal of Immunology
Volume30
Issue number3
DOIs
Publication statusPublished - 2000

Keywords

  • Immunomodulation
  • In vivo activated promoter
  • Salmonella aroA

ASJC Scopus subject areas

  • Immunology

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