Immunogenicity of immunoliposomes.
Multilamellar immunoliposomes were prepared from dipalmitoylphosphatidylcholine (DPPC), cholesterol (CH), sphingomyelin (SPH) and biotinylated dipalmitoylphosphatidylethanolamine (PEB) in the molar ratio of 1:1:1:0.1 with surface linked avidin-biotinylated sheep (anti-mouse IgG) IgG (AV-sIgGB) or GK1.5 monoclonal rat (antimouse L3T4 antigen) IgG (AV-GK1.5B). The ability of these immunoliposomes to induce antibody responses against AV, sIgG or GK1.5 was determined. GK1.5B and sIgGB elicited a low-level antibody response (5-10 microgram/ml serum) after i.v. immunization and boosting. Liposomes (1 mumol) containing GK1.5B or sIgGB were more effective than free GK1.5B or sIgGB in eliciting antibodies (20-30 and 100-120 micrograms/ml serum, respectively). Liposomal AV mixed with either sIgG or GK1.5 gave antibody levels comparable to immunization with free GK1.5B or sIgGB. Liposomes with surface AV-sIgGB or AV-GK1.5B elicited antibodies against AV and high levels against GK1.5 or sIgG. Immunoliposomes possessing surface AV-sIgGB or AV-GK1.5B were eliminated from the circulation of normal mice relatively slowly (T1/2 15.5 and 30 min): in contrast, liposomal AV-sIgGB or AV-GK1.5B was rapidly eliminated from the circulation of immunized mice (T1/2 4.5 and 4.0 min). These results demonstrate that liposomes with surface IgG (immunoliposomes) are immunogenic, and that repeated administration elicits anti-IgG antibodies that result in a significant reduction in blood circulation residence times.
Phillips
N C
NC
Montreal General Hospital Research Institute, Quebec, Canada.
Emili
A
A
D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000096:biosynthesis* / Q000276:immunology; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology; D001360:Avidin / Q000276:immunology; D006207:Half-Life; D007074:Immunoglobulin G / Q000008:administration & dosage / Q000276:immunology*; D008081:Liposomes / Q000493:pharmacokinetics; D008297:Male; D051379:Mice / Q000276:immunology; D051381:Rats / Q000276:immunology; D012756:Sheep / Q000276:immunology; D013047:Specific Pathogen-Free Organisms
D000888:Antibodies, Anti-Idiotypic; D000945:Antigens, Differentiation, T-Lymphocyte; D007074:Immunoglobulin G; D008081:Liposomes; D001360:Avidin