Arteriosclerosis, Thrombosis, and Vascular Biology. 2000;20:2106-2112
© 2000 American Heart Association, Inc.
Atherosclerosis and Lipoproteins |
Vaccine-Induced Antibodies Inhibit CETP Activity In Vivo and Reduce Aortic Lesions in a Rabbit Model of Atherosclerosis
From AVANT Immunotherapeutics, Inc, Needham, Mass, and Boston University Medical Center (A.D.C.), Boston, Mass.
Correspondence to Charles W. Rittershaus, AVANT Immunotherapeutics, Inc, 119 Fourth Ave, Needham, MA 02494. E-mail crittershaus{at}avantimmune.com
Abstract—Using a vaccine approach, we immunized New Zealand White rabbits with a peptide containing a region of cholesteryl ester transfer protein (CETP) known to be required for neutral lipid transfer function. These rabbits had significantly reduced plasma CETP activity and an altered lipoprotein profile. In a cholesterol-fed rabbit model of atherosclerosis, the fraction of plasma cholesterol in HDL was 42% higher and the fraction of plasma cholesterol in LDL was 24% lower in the CETP-vaccinated group than in the control-vaccinated group. Moreover, the percentage of the aorta surface exhibiting atherosclerotic lesion was 39.6% smaller in the CETP-vaccinated rabbits than in controls. The data reported here demonstrate that CETP activity can be reduced in vivo by vaccination with a peptide derived from CETP and support the concept that inhibition of CETP activity in vivo can be antiatherogenic. In addition, these studies suggest that vaccination against a self-antigen is a viable therapeutic strategy for disease management.
Key Words: CETP • lipoproteins • atherosclerosis • vaccine
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