Vaccine-induced antibodies inhibit CETP activity in vivo and reduce aorticlesions in a rabbit model of atherosclerosis

Using a vaccine approach, we immunized New Zealand White rabbits with a pep tide containing a region of cholesteryl ester transfer protein (CETP) known to be required for neutral lipid transfer function. These rabbits had sign ificantly reduced plasma CETP activity and an altered lipoprotein profile. In a cholesterol-fed rabbit model of atherosclerosis, the fraction of plasm a 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-vacci nated group. Moreover, the percentage of the aorta surface exhibiting ather osclerotic lesion was 39.6% smaller in the CETP-vaccinated rabbits than in controls. The data reported here demonstrate that CETP activity can be redu ced in vivo by vaccination with a peptide derived from CETP and support the concept that inhibition of CETP activity in vivo can be antiatherogenic. I n addition, these studies suggest that vaccination against a self-antigen i s a viable therapeutic strategy for disease management.