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-sIgG(B)) or GK1.5 monoclonal rat (anti-mouse L3T4 antigen) IgG (AV-GK1.5(B)). The ability of these immunoliposomes to induce antibody responses against AV, sIgG or GK1.5 was determined. GK1.5(B) and sIgG(B) elicited a low-level antibody response (5-10-mu-g/ml serum) after i.v. immunization and boosting. Liposomes (1-mu-mol) containing GK1.5(B) or sIgG(B) were more effective than free GK1.5(B) or sIgG(B) in eliciting antibodies (20-30 and 100-120-mu-g/ml serum, respectively). Liposomal AV mixed with either sIgG or GK1.5 gave antibody levels comparable to immunization with free GK1.5(B) or sIgG(B). Liposomes with surface AV-sIgG(B) or AV-GK1.5(B) elicited antibodies against AV and high levels against GK1.5 or sIgG. Immunoliposomes possessing surface AV-sIgG(B) or AV-GK1.5(B) were eliminated from the circulation of normal mice relatively slowly (T1/2 15.5 and 30 min): in contrast, liposomal AV-sIgG(B) or AV-GK1.5(B) 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.