Sterically stabilized cationic liposomes improve the uptake and immunostimulatory activity of CpG oligonucleotides.
Immunostimulatory CpG oligonucleotides (ODN) show promise as immune adjuvants, anti-allergens, and immunoprotective agents. Increasing the bioavailability and duration of action of CpG ODN should improve their therapeutic utility. Encapsulating ODN in sterically stabilized cationic liposomes provides protection from serum nucleases while facilitating uptake by B cells, dendritic cells, and macrophages. In a pathogen challenge model, sterically stabilized cationic liposomes encapsulation doubled the duration of CpG ODN-induced immune protection. In an immunization model, coencapsulation of CpG ODN with protein Ag (OVA) magnified the resultant Ag-specific IFN-gamma and IgG responses by 15- to 40-fold compared with Ag plus CpG ODN alone. These findings support the use of sterically stabilized cationic liposomes to significantly enhance the therapeutic efficacy of CpG ODN.
Gursel
I
I
Section of Retroviral Immunology, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD 20892, USA.
Gursel
M
M
Ishii
K J
KJ
Klinman
D M
DM
D000276:Adjuvants, Immunologic / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D000818:Animals; D017951:Antigen Presentation; D000941:Antigens / Q000276:immunology; D001202:Ascitic Fluid / Q000378:metabolism; D019013:CD40 Antigens / Q000096:biosynthesis / Q000235:genetics; D002412:Cations; D018899:CpG Islands; D004337:Drug Carriers; D004339:Drug Compounding; D057927:Hydrophobic and Hydrophilic Interactions; D007114:Immunization; D007274:Injections, Intraperitoneal; D007928:Lethal Dose 50; D008081:Liposomes / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D008089:Listeria monocytogenes / Q000276:immunology; D008088:Listeriosis / Q000276:immunology / Q000517:prevention & control; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000276:immunology; D013047:Specific Pathogen-Free Organisms; D013154:Spleen / Q000378:metabolism
D000276:Adjuvants, Immunologic; D000941:Antigens; D019013:CD40 Antigens; D002412:Cations; D004337:Drug Carriers; D008081:Liposomes; D010047:Ovalbumin