Use of CpG oligodeoxynucleotides as immunoprotective agents.
Single-stranded oligodeoxynucleotides (ODNs) synthesised to express unmethylated 'CpG motifs' mimic the ability of bacterial DNA to trigger the innate immune system. CpG ODNs stimulate cells that express Toll-like receptor 9, initiating an immunomodulatory cascade resulting in the activation of B and T lymphocytes, natural killer cells, monocytes, macrophages and dendritic cells. CpG ODNs improve the host's ability to resist infection by accelerating and improving the induction of an innate and then adaptive immune response, characterised by the production of Th1 and pro-inflammatory cytokines, chemokines and polyreactive antibodies. Studies in rodents and non-human primates demonstrate that CpG ODNs can protect the host against bacterial, viral, fungal and parasitic infections. CpG-induced protection develops rapidly but persists for only a few weeks. Preclinical and clinical trials suggest that CpG ODNs can be used safely to activate the human immune system.
Klinman
Dennis M
DM
Section of Retroviral Immunology, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD 20892, USA. Klinman@cber.fda.gov
D000276:Adjuvants, Immunologic / Q000627:therapeutic use*; D000818:Animals; D018925:Chemokines / Q000378:metabolism; D018899:CpG Islands; D016207:Cytokines / Q000378:metabolism; D004269:DNA, Bacterial / Q000235:genetics; D004268:DNA-Binding Proteins / Q000378:metabolism; D006801:Humans; D007113:Immunity, Innate; D007700:Kinetics; D051379:Mice; D008954:Models, Biological; D009838:Oligodeoxyribonucleotides / Q000737:chemistry* / Q000494:pharmacology; D011956:Receptors, Cell Surface / Q000378:metabolism; D013997:Time Factors; D051217:Toll-Like Receptor 9
D000276:Adjuvants, Immunologic; C408982:CPG-oligonucleotide; D018925:Chemokines; D016207:Cytokines; D004269:DNA, Bacterial; D004268:DNA-Binding Proteins; D009838:Oligodeoxyribonucleotides; D011956:Receptors, Cell Surface; C495371:TLR9 protein, human; C495370:Tlr9 protein, mouse; D051217:Toll-Like Receptor 9