Immunoregulatory activity of CpG oligonucleotides in humans and nonhuman primates.
Oligodeoxynucleotides (ODN) containing CpG motifs mimic the ability of microbial DNA to activate the innate immune system. The resultant response limits the early spread of infectious organisms while promoting the development of adaptive immunity. CpG ODN show promise as vaccine adjuvants and in the treatment of asthma, allergy, infection, and cancer. Due to evolutionary divergence in CpG recognition between species, CpG ODN that are most active in rodents are poorly immunostimulatory in primates. Thus, evidence that CpG ODN have therapeutic activity in mice must be confirmed in primates. Two distinct types of CpG ODN were identified that stimulate primate PBMC. D-type ODN trigger plasmacytoid DC to secrete IFNalpha, monocytes to mature into functionally active DC, and NK cells to secrete IFNgamma. K-type ODN stimulate B cells and monocytes to proliferate and secrete IgM, IL-10, and/or IL-6. In vivo studies in nonhuman primates indicate that proinflammatory or humoral immune responses can be selectively facilitated by judicious use of these distinct types of ODN.
Division of Therapeutic Proteins, Food and Drug Administration, Building 29A Room 3B19, 8800 Rockville Pike, Bethesda, MD 20892, USA.
Daniela
D
Verthelyi
Dennis M
DM
Klinman
D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000818:Animals; D001249:Asthma / Q000188:drug therapy; D001483:Base Sequence; D006801:Humans; D006967:Hypersensitivity / Q000188:drug therapy; D007113:Immunity, Innate / Q000187:drug effects; D008213:Lymphocyte Activation / Q000187:drug effects; D009369:Neoplasms / Q000188:drug therapy; D009838:Oligodeoxyribonucleotides / Q000235:genetics / Q000276:immunology / Q000494:pharmacology*; D011323:Primates; D012449:Safety; D014612:Vaccines / Q000008:administration & dosage
D000276:Adjuvants, Immunologic; C408982:CPG-oligonucleotide; D009838:Oligodeoxyribonucleotides; D014612:Vaccines