Approaches to enhancing immune responses stimulated by CpG oligodeoxynucleotides.
CpG oligodeoxynucleotides (ODN) activate the immune system and are promising immunotherapeutic agents against infectious diseases, allergy/asthma and cancer. It has become apparent that while CpG ODN are potent immune activators in mice, their immune stimulatory effects are often less dramatic in humans and large animals. This disparity between rodents and mammals has been attributed to the differences in TLR9 expression in different species. This along with the sometimes transient activity of ODN may limit its potential immunotherapeutic applications. Several approaches to enhance the activity of CpG ODN have been explored including formulation of ODN in depot-forming adjuvants, and more recently, coadministration with polyphosphazenes, inhibitors of cytokines that downregulate TLR9 activation, and simultaneous activation with multiple TLR agonists. We will discuss these approaches and the mechanisms involved, with emphasis on what we have learned from large animal models.
Mutwiri
George
G
Vaccine & Infectious Disease Organization/International Vaccine Center, University of Saskatchewan, SK, Canada. george.mutwiri@usask.ca
van Drunen Littel-van den Hurk
Sylvia
S
Babiuk
Lorne A
LA
D000276:Adjuvants, Immunologic / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D000818:Animals; D001428:Bacterial Vaccines / Q000008:administration & dosage / Q000276:immunology; D018899:CpG Islands; D004339:Drug Compounding; D006801:Humans; D007110:Immunity, Active / Q000187:drug effects; D007113:Immunity, Innate / Q000187:drug effects; D009838:Oligodeoxyribonucleotides / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D009943:Organophosphorus Compounds / Q000008:administration & dosage; D011108:Polymers / Q000008:administration & dosage; D051217:Toll-Like Receptor 9 / Q000819:agonists; D014765:Viral Vaccines / Q000008:administration & dosage / Q000276:immunology
D000276:Adjuvants, Immunologic; D001428:Bacterial Vaccines; C408982:CPG-oligonucleotide; D009838:Oligodeoxyribonucleotides; D009943:Organophosphorus Compounds; D011108:Polymers; D051217:Toll-Like Receptor 9; D014765:Viral Vaccines; C108974:poly(phosphazene)