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Clinical and Vaccine Immunology, August 2007, p. 952-958, Vol. 14, No. 8
1071-412X/07/$08.00+0     doi:10.1128/CVI.00119-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

The Bacterial Second Messenger cdiGMP Exhibits Promising Activity as a Mucosal Adjuvant{triangledown}

Thomas Ebensen, Kai Schulze, Peggy Riese, Michael Morr, and Carlos A. Guzmán*

Department of Vaccinology, Helmholtz Centre for Infection Research, D-38124 Braunschweig, Germany

Received 13 March 2007/ Returned for modification 18 April 2007/ Accepted 31 May 2007

The 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.

* Corresponding author. Mailing address: Department of Vaccinology, Helmholtz Centre for Infection Research, Inhoffenstrasse 7, D-38124 Braunschweig, Germany. Phone: 49 531 61814600. Fax: 49 531 61814699. E-mail: carlos.guzman{at}helmholtz-hzi.de

{triangledown} Published ahead of print on 13 June 2007.

Clinical and Vaccine Immunology, August 2007, p. 952-958, Vol. 14, No. 8
1071-412X/07/$08.00+0     doi:10.1128/CVI.00119-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.





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