Enhanced desensitization efficacy by liposomal conjugation of a specific antigen.
Since liposomes are known as strong adjuvants, we attempted to use liposomes in immunotherapy as adjuvants, and to achieve desensitization in pre-sensitized mice. At first, we sensitized mice with intraperitoneal injection of model antigen, 100 microg ovalbumin (OVA), with Alum and treated them with liposome composed of distearoylphosphatidylcholine (DSPC) and cholesterol (2:1 as a molar ratio), which was coupled with a small amount of OVA (10 microg OVA in 400 nmol DSPC and 200 nmol cholesterol-liposome was injected into 20 g mouse). It is well known that antigen-specific immunotherapy increases IgG blocking antibodies and decreases in IgE antibodies. The treatment with i.v. injection of OVA-liposome at days 8, 10, and 12 after sensitization strongly suppressed OVA-specific IgE production without affecting IgG level after the boost (100 microg OVA with Alum). Moreover, the treatment with high-density OVA-liposome (10 microg OVA in 80 nmol DSPC and 40 nmol cholesterol-liposome/20 g mouse) not only strongly suppressed IgE levels but also reduced IgG production after the boost of OVA-sensitized mice suggesting the importance of liposomal characteristic in desensitization immunotherapy. Next we reduced the dose of OVA-liposome and the desensitization effect was also observed at the dose of as low as 1 microg OVA on OVA-liposome/mouse. On the contrary, free OVA did not affect the production of both IgG and IgE levels. Biodistribution study indicated that OVA-liposome was highly accumulated in spleen of OVA-sensitized mice compared to control liposome at 3 h after i.v. injection. These results suggest that the liposomal OVA effectively interacts with and desensitizes immune cells, therefore, liposomes coupling with a certain antigen may be effective in allergy immunotherapy.
Ichikawa
K
K
Department of Medical Biochemistry and COE Program in the 21st Century, University or Shizuoka School of Pharmaceutical Sciences, 52-1 Yada, Suruga-ku, Shizuoka 422-8526, Japan.
Urakami
T
T
Yonezawa
S
S
Miyauchi
H
H
Shimizu
K
K
Asai
T
T
Oku
N
N
D000276:Adjuvants, Immunologic / Q000493:pharmacokinetics / Q000494:pharmacology*; D000534:Alum Compounds; D000818:Animals; D000941:Antigens / Q000008:administration & dosage / Q000276:immunology* / Q000494:pharmacology; D002784:Cholesterol; D003888:Desensitization, Immunologic; D004306:Dose-Response Relationship, Immunologic; D004334:Drug Administration Schedule; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006967:Hypersensitivity / Q000188:drug therapy / Q000276:immunology; D007073:Immunoglobulin E / Q000187:drug effects / Q000378:metabolism*; D007074:Immunoglobulin G / Q000187:drug effects / Q000378:metabolism; D008081:Liposomes; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology* / Q000493:pharmacokinetics / Q000494:pharmacology; D010713:Phosphatidylcholines; D013154:Spleen / Q000378:metabolism; D014018:Tissue Distribution
D000276:Adjuvants, Immunologic; D000534:Alum Compounds; D000941:Antigens; D007074:Immunoglobulin G; D008081:Liposomes; D010713:Phosphatidylcholines; C041524:aluminum sulfate; D007073:Immunoglobulin E; D010047:Ovalbumin; D002784:Cholesterol; C010942:1,2-distearoyllecithin