| Autor: |
Ebensen, Thomas, Schulze, Kai, Riese, Peggy, Morr, Michael, Guzma´n, Carlos A. |
| Zdroj: |
Clinical and Vaccine Immunology (formerly CDLI); August 2007, Vol. 14 Issue: 8 p952-958, 7p |
| Abstrakt: |
ABSTRACTThe development of mucosal adjuvants is still a critical need in vaccinology. In the present work, we show that bis(3',5')-cyclic dimeric GMP (cdiGMP), a second messenger that modulates cell surface properties of several microorganisms, exerts potent activity as a mucosal adjuvant. BALB/c mice were immunized intranasally with the model antigen ß-galactosidase (ß-Gal) coadministered with cdiGMP. Animals receiving cdiGMP as an adjuvant showed significantly higher anti-ß-Gal immunoglobulin G (IgG) titers in sera than controls (i.e., 512-fold [P< 0.05]). Coadministration of cdiGMP also stimulated efficient ß-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 ß-Gal protein and a peptide encompassing its major histocompatibility complex class I-restricted epitope. The IgG1-to-IgG2a ratio of anti-ß-Gal antibodies and the observed profiles of secreted cytokines suggest that a dominant Th1 response pattern is promoted by mucosal coadministration of cdiGMP. Finally, the use of cdiGMP as a mucosal adjuvant also led to the stimulation of in vivo cytotoxic T-lymphocyte responses in C57BL/6 mice intranasally immunized with ovalbumin and cdiGMP (up to 30% of specific lysis). The results obtained indicate that cdiGMP is a promising tool for the development of mucosal vaccines. |
| Databáze: |
Supplemental Index |
| Externí odkaz: |
|
