The bacterial second messenger cdiGMP exhibits promising activity as mucosal adjuvant

نویسندگان

  • Thomas Ebensen
  • Kai Schulze
  • Peggy Riese
  • Michael Morr
  • Carlos A. Guzman
چکیده

The bacterial second messenger cdiGMP exhibits promising activity as a mucosal adjuvant. Abstract The development of mucosal adjuvants is still a critical need in vaccinology. In the present work we show that bis-(3′,5′)-cyclic dimeric guanosine monophosphate (cdiGMP), a second messenger that modulates cell surface properties of several microorganisms , exerts potent activity as mucosal adjuvant. BALB/c mice were immunized by intranasal route with the model antigen beta-Galactosidase (beta-Gal) co-administered with cdiGMP. Animals receiving cdiGMP as adjuvant showed significantly higher anti-beta-Gal immunoglobulin G (IgG) titers in sera than controls (i.e. 512-fold; p<0.05). Co-administration of cdiGMP also stimulated efficient beta-Gal-specific secretory IgA production in the lung (p<0.016) and vagina (p<0.036). Cellular immune responses were observed in response to both the beta-Gal protein and a peptide encompassing its MHC class I-restricted epitope. The IgG1/IgG2a ratio of anti-beta-Gal antibodies and the observed profiles of secreted cytokines suggest that a dominant Th1 response pattern is promoted by mucosal co-administration of cdiGMP. Finally, the use of cdiGMP as mucosal adjuvant also lead to the stimulation of in vivo CTL responses in C57Bl6 mice intranasally immunized with ovalbumin and cdiGMP (up to 30% of specific lysis). The obtained results indicate that cdiGMP is a promising tool for the development of mucosal vaccines.

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The bacterial second messenger cdiGMP exhibits promising activity as a mucosal adjuvant.

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تاریخ انتشار 2008