Vaccinating Rabbits with a Cholesteryl Ester Transfer Protein (CETP) B-Cell Epitope Carried by Heat Shock Protein-65 (HSP65) for Inducing Anti-CETP Antibodies and Reducing Aortic Lesions In Vivo

Abstract

Rabbits were vaccinated with a recombinant protein vaccine of HSP65-CETPC comprising mycobacterial heat shock protein-65 (HSP65) and a cholesteryl ester transfer protein (CETP) B-cell epitope in alum adjuvant for inducing anti-CETP antibodies in vivo. After anti-CETP antibodies were successfully produced, rabbits were fed with a high-cholesterol diet for 15 weeks, and then the antiatherogenic effects of anti-CETP antibodies were evaluated. The results showed that the fraction of plasma cholesterol in HDL increased and the fraction of plasma cholesterol in LDL decreased in rHSP65-CETPC-immunized rabbits when compared with those in control animals. The average percentage of aortic lesions in the entire aorta area in rHSP65-CETPC-vaccinated rabbits was 23.8% less than in OVA-immunized rabbits (15.14% vs 19.86%) and 30.8% less than in rHSP65 immunized rabbits (15.14% vs 21.87%). The average thickness of hyperplastic coronary artery in rHSP65-CETPC immunized rabbits was 164 +/- 12 microm, significantly lower than in rHSP65-immunized rabbits (197 +/- 15 microm) and in OVA-immunized rabbits (206 +/- 15 microm). Taken together, vaccination with the rHSP65-CETPC vaccine could significantly attenuate atherosclerosis in a rabbit model. Thus, the chimeric protein of rHSP65-CETPC can be further developed into an antiatherosclerosis vaccine in the future.