Immunostimulatory CpG oligonucleotides: Effect on gene expression and utility as vaccine adjuvants

Dennis M. Klinman, Sven Klaschik, Koji Tomaru, Hidekazu Shirota, Debra Tross, Hidekazu Ikeuchi

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

Synthetic oligodeoxynucleotides (ODN) containing unmethylated CpG motifs mimic the immunostimulatory activity of bacterial DNA. CpG ODN directly stimulate B cells and plasmacytoid dendritic cells (pDC), promote the production of Th1 and pro-inflammatory cytokines, and trigger the maturation/activation of professional antigen presenting cells. CpG ODN are finding use as vaccine adjuvants, where they increase the speed, magnitude and duration of vaccine-specific immune responses. For example, CpG ODN significantly prolong the protection induced by AVA (Anthrax Vaccine Adsorbed). Unexpectedly, a majority of animals immunized with CpG-adjuvanted AVA maintain resistance to anthrax infection even after their Ab titers decline to sub-protective levels. This survival is mediated by the de novo production of protective Abs by high affinity long-lived memory B cells. The immunostimulatory activity of CpG ODN was probed at the molecular level by microarray. Results show that a small group of 'inducers' rapidly up-regulated a large network genes following CpG treatment of mice. This stimulatory activity is quenched by 'suppressors' that down-regulate the expression of targeted genes, including most of the 'inducers'. These findings shed light on the mechanism underlying CpG-mediated immune activation and therapeutic activity.

Original languageEnglish
Pages (from-to)1919-1923
Number of pages5
JournalVaccine
Volume28
Issue number8
DOIs
Publication statusPublished - 2010 Feb 23
Externally publishedYes

Keywords

  • Adaptive immunity
  • CpG oligonucleotide
  • Innate immunity
  • Microarray
  • Regulation
  • Vaccine adjuvant

ASJC Scopus subject areas

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

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