IMMUNIZATION WITH CHOLESTEROL-RICH LIPOSOMES INDUCES ANTI-CHOLESTEROLANTIBODIES AND REDUCES DIET-INDUCED HYPERCHOLESTEROLEMIA AND PLAQUE-FORMATION

Immunization of rabbits with a protein-free formulation consisting of liposomes containing 71% cholesterol and lipid A as an adjuvant induce d anticholesterol antibodies that caused complement-dependent lysis of liposomes lacking lipid A. The antibodies, immunoglobulin G (IgG) and immunoglobulin M (IgM), also recognized nonoxidized crystalline chole sterol as an antigen by enzyme-linked immunosorbent assay (ELISA). The effects of immunization against cholesterol on elevations in serum ch olesterol and development of atherosderosis were examined in rabbits f ed a diet containing 0.5% to 1.0% cholesterol. Although the mean serum cholesterol level, mainly in the form of very-low-density lipoprotein cholesterol, rose as much as 60-fold in the nonimmunized rabbits, the elevation was significantly less-as much as 35% lower-in the immunize d rabbits. Elevation of serum cholesterol was accompanied by an appare nt drop in the level of antibodies on initiating the diet, followed by a rebound on stopping the diet, thus suggesting that the antibodies w ere adsorbed to cholesterol that was present in circulating lipoprotei ns. When lipoprotein fractions-composed of either very-low-density and intermediate-density lipoproteins derived from cholesterol-fed nonimm unized rabbits or human low-density lipoproteins-were tested as captur e antigens by solid-phase ELISA, reactivity was observed with IgG and IgM antibodies present in the serum of immunized rabbits. Immunization also resulted in a marked decrease in the risk of developing atherosc lerosis. Analysis of aortic atherosclerosis by quantitative histologic examination and fatty streaks by automated morphometric probability-o f-occurrence mapping showed diminished atherosclerosis in most areas o f the aorta in vaccine recipients. It is proposed that immunization wi th liposomes containing 71% cholesterol and lipid A can reduce diet-in duced hypercholesterolemia and atherosclerosis.