Immunization with cholesterol-rich liposomes induces anti-cholesterol antibodies 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 induced 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 cholesterol as an antigen by enzyme-linked immunosorbent assay (ELISA). The effects of immunization against cholesterol on elevations in serum cholesterol and development of atherosclerosis were examined in rabbits fed 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 immunized rabbits. Elevation of serum cholesterol was accompanied by an apparent drop in the level of antibodies on initiating the diet, followed by a rebound on stopping the diet, thus suggesting that the antibodies were adsorbed to cholesterol that was present in circulating lipoproteins. When lipoprotein fractions--composed of either very-low-density and intermediate-density lipoproteins derived from cholesterol-fed nonimmunized rabbits or human low-density lipoproteins--were tested as capture 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 atherosclerosis. Analysis of aortic atherosclerosis by quantitative histologic examination and fatty streaks by automated morphometric probability-of-occurrence mapping showed diminished atherosclerosis in most areas of the aorta in vaccine recipients. It is proposed that immunization with liposomes containing 71% cholesterol and lipid A can reduce diet-induced hypercholesterolemia and atherosclerosis.
Alving
C R
CR
Department of Membrane Biochemistry, Walter Reed Army Institute of Research, Washington, DC 20307-5100, USA.
Swartz
G M
GM
Wassef
N M
NM
Ribas
J L
JL
Herderick
E E
EE
Virmani
R
R
Kolodgie
F D
FD
Matyas
G R
GR
Cornhill
J F
JF
D000818:Animals; D000906:Antibodies / Q000276:immunology*; D000917:Antibody Formation; D001161:Arteriosclerosis / Q000276:immunology / Q000473:pathology / Q000517:prevention & control; D002784:Cholesterol / Q000008:administration & dosage / Q000097:blood / Q000276:immunology*; D002791:Cholesterol, Dietary / Q000009:adverse effects*; D004337:Drug Carriers; D006937:Hypercholesterolemia / Q000209:etiology / Q000473:pathology* / Q000628:therapy*; D007114:Immunization; D008074:Lipoproteins / Q000276:immunology; D053419:Lipoproteins, IDL; D008079:Lipoproteins, VLDL / Q000276:immunology; D008081:Liposomes; D011817:Rabbits
D000906:Antibodies; D002791:Cholesterol, Dietary; D004337:Drug Carriers; D008074:Lipoproteins; D053419:Lipoproteins, IDL; D008079:Lipoproteins, VLDL; D008081:Liposomes; D002784:Cholesterol