Enhancement of infectious disease vaccines through TLR9-dependent recognition of CpG DNA.
The adaptive immune system-with its remarkable ability to generate antigen-specific antibodies and T lymphocytes against pathogens never before "seen" by an organism-is one of the marvels of evolution. However, to generate these responses, the adaptive immune system requires activation by the innate immune system. Toll-like receptors (TLRs) are perhaps the best-understood family of innate immune receptors for detecting infections and stimulating adaptive immune responses. TLR9 appears to have evolved to recognize infections by a subtle structural difference between eukaryotic and prokaryotic/viral DNA; only the former frequently methylates CpG dinucleotides. Used as vaccine adjuvants, synthetic oligodeoxynucleotide (ODN) ligands for TLR9--CpG ODN--greatly enhance the speed and strength of the immune responses to vaccination.
McCluskie
M J
MJ
Coley Pharmaceutical Group, Inc., 93 Worcester Street, Suite 101, Wellesley, MA 02481, USA.
Krieg
A M
AM
D000276:Adjuvants, Immunologic; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D001424:Bacterial Infections / Q000276:immunology; D018899:CpG Islands / Q000276:immunology*; D004269:DNA, Bacterial / Q000235:genetics; D004279:DNA, Viral / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007110:Immunity, Active; D008024:Ligands; D009838:Oligodeoxyribonucleotides / Q000138:chemical synthesis / Q000235:genetics / Q000276:immunology; D051217:Toll-Like Receptor 9 / Q000276:immunology* / Q000378:metabolism; D014612:Vaccines / Q000276:immunology*; D014777:Virus Diseases / Q000276:immunology
D000276:Adjuvants, Immunologic; D004269:DNA, Bacterial; D004279:DNA, Viral; D008024:Ligands; D009838:Oligodeoxyribonucleotides; D051217:Toll-Like Receptor 9; D014612:Vaccines