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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 |
Published version: | http://dx.doi.org/10.1016/j.vaccine.2008.06.099 |
Appears in Collections: | Aurora harvest 5 Molecular and Biomedical Science publications |
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