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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
Statement of
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
Mice, Inbred BALB C
Streptococcus pneumoniae
Pneumococcal Infections
Alum Compounds
Bacterial Proteins
Cyclic GMP
Pneumococcal Vaccines
Immunologic Factors
Adjuvants, Immunologic
Antibodies, Bacterial
Colony Count, Microbial
Administration, Intranasal
Injections, Intraperitoneal
Survival Analysis
Description: Copyright © 2008 Elsevier Ltd All rights reserved.
DOI: 10.1016/j.vaccine.2008.06.099
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Appears in Collections:Aurora harvest 5
Molecular and Biomedical Science publications

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