期刊
VACCINE
卷 26, 期 36, 页码 4676-4685出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.vaccine.2008.06.099
关键词
Streptococcus pneumoniae; c-di-GMP; immunomodulator; adjuvant; vaccine
资金
- Army Research Office
- National Health and Medical Research Council [284214]
- Welcome Trust [075846]
- MRC [G981148]
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 all effective broad spectrum immunomodulator and vaccine adjuvant to prevent infectious diseases. (C) 2008 Elsevier Ltd. All rights reserved.
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