2.50
Hdl Handle:
http://hdl.handle.net/10033/18940
Title:
The bacterial second messenger cdiGMP exhibits promising activity as a mucosal adjuvant.
Authors:
Ebensen, Thomas ( 0000-0001-8906-063X ) ; Schulze, Kai ( 0000-0003-2286-3416 ) ; Riese, Peggy ( 0000-0001-6796-6780 ) ; Morr, Michael; Guzmán, Carlos A
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 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 beta-galactosidase (beta-Gal) coadministered with cdiGMP. Animals receiving cdiGMP as an adjuvant showed significantly higher anti-beta-Gal immunoglobulin G (IgG) titers in sera than controls (i.e., 512-fold [P < 0.05]). Coadministration 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 major histocompatibility complex class I-restricted epitope. The IgG1-to-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 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.
Affiliation:
Department of Vaccinology, Helmholtz Centre for Infection Research, Inhoffenstrasse 7, D-38124 Braunschweig, Germany.
Citation:
The bacterial second messenger cdiGMP exhibits promising activity as a mucosal adjuvant. 2007, 14 (8):952-8 Clin. Vaccine Immunol.
Journal:
Clinical and vaccine immunology : CVI
Issue Date:
Aug-2007
URI:
http://hdl.handle.net/10033/18940
DOI:
10.1128/CVI.00119-07
PubMed ID:
17567766
Type:
Article
Language:
en
ISSN:
1556-6811
Appears in Collections:
publications of the research group vaccinology and applied microbiology (VAC)

Full metadata record

DC FieldValue Language
dc.contributor.authorEbensen, Thomasen
dc.contributor.authorSchulze, Kaien
dc.contributor.authorRiese, Peggyen
dc.contributor.authorMorr, Michaelen
dc.contributor.authorGuzmán, Carlos Aen
dc.date.accessioned2008-02-22T09:37:33Zen
dc.date.available2008-02-22T09:37:33Zen
dc.date.issued2007-08en
dc.identifier.citationThe bacterial second messenger cdiGMP exhibits promising activity as a mucosal adjuvant. 2007, 14 (8):952-8 Clin. Vaccine Immunol.en
dc.identifier.issn1556-6811en
dc.identifier.pmid17567766en
dc.identifier.doi10.1128/CVI.00119-07en
dc.identifier.urihttp://hdl.handle.net/10033/18940en
dc.description.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 beta-galactosidase (beta-Gal) coadministered with cdiGMP. Animals receiving cdiGMP as an adjuvant showed significantly higher anti-beta-Gal immunoglobulin G (IgG) titers in sera than controls (i.e., 512-fold [P < 0.05]). Coadministration 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 major histocompatibility complex class I-restricted epitope. The IgG1-to-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 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.en
dc.language.isoenen
dc.subject.meshAdjuvants, Immunologicen
dc.subject.meshAdministration, Intranasalen
dc.subject.meshAnimalsen
dc.subject.meshCyclic GMPen
dc.subject.meshCytotoxicity, Immunologicen
dc.subject.meshFemaleen
dc.subject.meshImmunity, Mucosalen
dc.subject.meshImmunizationen
dc.subject.meshImmunoglobulin A, Secretoryen
dc.subject.meshImmunoglobulin Gen
dc.subject.meshLungen
dc.subject.meshLymphocyte Activationen
dc.subject.meshMiceen
dc.subject.meshMice, Inbred BALB Cen
dc.subject.meshMice, Inbred C57BLen
dc.subject.meshOvalbuminen
dc.subject.meshSecond Messenger Systemsen
dc.subject.meshT-Lymphocytes, Cytotoxicen
dc.subject.meshVaginaen
dc.subject.meshbeta-Galactosidaseen
dc.titleThe bacterial second messenger cdiGMP exhibits promising activity as a mucosal adjuvant.en
dc.typeArticleen
dc.contributor.departmentDepartment of Vaccinology, Helmholtz Centre for Infection Research, Inhoffenstrasse 7, D-38124 Braunschweig, Germany.en
dc.identifier.journalClinical and vaccine immunology : CVIen

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