c-di-GMP is an effective immunomodulator and vaccine adjuvant against pneumococcal infection

Abiodun D. Ogunniyi, James C. Paton, Alun C. Kirby, Jonathan Mccullers, Jan Cook, Mamoru Hyodo, Yoshihiro Hayakawa, David K.R. Karaolis

Research output: Contribution to journalArticle

51 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)4676-4685
Number of pages10
JournalVaccine
Volume26
Issue number36
DOIs
StatePublished - Aug 26 2008

Fingerprint

Pneumococcal Infections
vaccine adjuvants
immunomodulators
Immunologic Factors
Vaccines
lungs
surface proteins
mice
serotypes
pretreatment
infection
Streptococcus pneumoniae
alum
toxoids
bacterial infections
infectious diseases
adjuvants
lymph nodes
Innate Immunity
Lung

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Immunology and Microbiology(all)
  • veterinary(all)
  • Public Health, Environmental and Occupational Health
  • Infectious Diseases

Cite this

Ogunniyi, A. D., Paton, J. C., Kirby, A. C., Mccullers, J., Cook, J., Hyodo, M., ... Karaolis, D. K. R. (2008). c-di-GMP is an effective immunomodulator and vaccine adjuvant against pneumococcal infection. Vaccine, 26(36), 4676-4685. https://doi.org/10.1016/j.vaccine.2008.06.099

c-di-GMP is an effective immunomodulator and vaccine adjuvant against pneumococcal infection. / Ogunniyi, Abiodun D.; Paton, James C.; Kirby, Alun C.; Mccullers, Jonathan; Cook, Jan; Hyodo, Mamoru; Hayakawa, Yoshihiro; Karaolis, David K.R.

In: Vaccine, Vol. 26, No. 36, 26.08.2008, p. 4676-4685.

Research output: Contribution to journalArticle

Ogunniyi, AD, Paton, JC, Kirby, AC, Mccullers, J, Cook, J, Hyodo, M, Hayakawa, Y & Karaolis, DKR 2008, 'c-di-GMP is an effective immunomodulator and vaccine adjuvant against pneumococcal infection', Vaccine, vol. 26, no. 36, pp. 4676-4685. https://doi.org/10.1016/j.vaccine.2008.06.099
Ogunniyi, Abiodun D. ; Paton, James C. ; Kirby, Alun C. ; Mccullers, Jonathan ; Cook, Jan ; Hyodo, Mamoru ; Hayakawa, Yoshihiro ; Karaolis, David K.R. / c-di-GMP is an effective immunomodulator and vaccine adjuvant against pneumococcal infection. In: Vaccine. 2008 ; Vol. 26, No. 36. pp. 4676-4685.
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