Enhanced immune response to T-independent antigen by using CpG oligodeoxynucleotides encapsulated in liposomes.
Immunostimulatory CpG oligodeoxynucleotides (ODN) have been tested as immunoadjuvants for various vaccines including T-cell independent (TI) antigens. Findings from previous reports suggest that close physical association of CpG ODN to the antigen could enhance its adjuvant effect. As an alternative to chemical conjugation of CpG ODN to the antigen, the current study is aimed at determining the benefit of using liposomes as a carrier for CpG ODN to improve the immune response to biotinylated liposomes (Bx-liposomes), a model of a TI antigen. Liposomes with suboptimal concentration of hapten (1% biotin) were not immunogenic. However, when CpG ODN encapsulated in Bx-liposomes were used to immunize mice, a hapten-specific response was obtained as indicated by antibody-mediated elimination of re-administered Bx-liposomes. CpG ODN co-administered with empty Bx-liposomes could not achieve the same effect, indicating the requirement for encapsulation of the adjuvant. Using both intravenous (i.v.) and subcutaneous (s.c.) immunization methods, it was found that IgM levels, but not IgG levels were elevated. Immunization in nude mice confirmed that the immune response obtained was TI. The use of non-CpG ODN and an ODN with alternatively flanked CpG motifs showed no adjuvant effect. Incorporation of poly(ethylene)glycol (PEG)-modified lipid in liposomes enhanced the immune response even further. In conclusion, our data shows that liposomes are a useful delivery vehicle for CpG ODN as an immune adjuvant for TI antigens.
Li
W M
WM
Department of Pathology and Laboratory Medicine, Faculty of Medicine, The University of British Columbia, BC, V5Z 1L3, Vancouver, Canada. mli@bccancer.bc.ca
Bally
M B
MB
Schutze-Redelmeier
M P
MP
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D000955:Antigens, T-Independent / Q000276:immunology*; D001710:Biotin / Q000276:immunology; D018899:CpG Islands / Q000276:immunology*; D004337:Drug Carriers; D004339:Drug Compounding; D006241:Haptens / Q000276:immunology; D007074:Immunoglobulin G / Q000032:analysis; D007075:Immunoglobulin M / Q000096:biosynthesis* / Q000276:immunology; D008081:Liposomes; D051379:Mice; D008819:Mice, Nude; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology; D010714:Phosphatidylethanolamines / Q000276:immunology; D011092:Polyethylene Glycols / Q000008:administration & dosage; D013873:Thionucleotides / Q000494:pharmacology; D014611:Vaccination
D000276:Adjuvants, Immunologic; D000955:Antigens, T-Independent; D004337:Drug Carriers; D006241:Haptens; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D008081:Liposomes; D009838:Oligodeoxyribonucleotides; D010714:Phosphatidylethanolamines; D013873:Thionucleotides; C038089:1,2-distearoylphosphatidylethanolamine; D011092:Polyethylene Glycols; D001710:Biotin