Please use this identifier to cite or link to this item: https://hdl.handle.net/2440/53330
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Type: Journal article
Title: C-di-GMP is an effective immunomodulator and vaccine adjuvant against pneumococcal infection
Author: Ogunniyi, A.
Paton, J.
Kirby, A.
McCullers, J.
Cook, J.
Hyodo, M.
Hayakawa, Y.
Karaolis, D.
Citation: Vaccine, 2008; 26(36):4676-4685
Publisher: Elsevier Sci Ltd
Issue Date: 2008
ISSN: 0264-410X
1873-2518
Statement of
Responsibility: 
Abiodun D. Ogunniyi, James C. Paton, Alun C. Kirby, Jonathan A. McCullers, Jan Cook, Mamoru Hyodo, Yoshihiro Hayakawa and David K.R. Karaolis
Abstract: Cyclic diguanylate (c-di-GMP) is a unique bacterial intracellular signaling molecule capable of stimulating enhanced protective innate immunity against various bacterial infections. The effects of intranasal pretreatment with c-di-GMP, or intraperitoneal coadministration of c-di-GMP with the pneumolysin toxoid (PdB) or pneumococcal surface protein A (PspA) before pneumococcal challenge, were investigated in mice. We found that c-di-GMP had no significant direct short-term effect on the growth rate of Streptococcus pneumoniae either in vitro or in vivo. However, intranasal pretreatment of mice with c-di-GMP resulted in a significant decrease in bacterial load in lungs and blood after serotypes 2 and 3 challenge, and a significant decrease in lung titers after serotype 4 challenge. Potential cellular mediators of these enhanced protective responses were identified in lungs and draining lymph nodes. Intraperitoneal coadministration of c-di-GMP with PdB or PspA before challenge resulted in significantly higher antigen-specific antibody titers and increased survival of mice, compared to that obtained with alum adjuvant. These findings demonstrate that local or systemic c-di-GMP administration stimulates innate and adaptive immunity against invasive pneumococcal disease. We propose that c-di-GMP can be used as an effective broad spectrum immunomodulator and vaccine adjuvant to prevent infectious diseases.
Keywords: Lung
Lymph Nodes
Blood
Animals
Mice, Inbred BALB C
Mice
Streptococcus pneumoniae
Pneumococcal Infections
Alum Compounds
Bacterial Proteins
Cyclic GMP
Streptolysins
Pneumococcal Vaccines
Immunologic Factors
Adjuvants, Immunologic
Antibodies, Bacterial
Colony Count, Microbial
Administration, Intranasal
Injections, Intraperitoneal
Survival Analysis
Female
Male
Description: Copyright © 2008 Elsevier Ltd All rights reserved.
DOI: 10.1016/j.vaccine.2008.06.099
Grant ID: http://purl.org/au-research/grants/nhmrc/284214
Description (link): http://www.elsevier.com/wps/find/journaldescription.cws_home/30521/description#description
Appears in Collections:Aurora harvest 5
Molecular and Biomedical Science publications

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