Intramuscular immunization with a DNA vaccine encoding a 26-amino acid CETP epitope displayed by HBc protein and containing CpG DNA inhibits atherosclerosis in a rabbit model of atherosclerosis

Rabbits were intramuscularly immunized with the plasmid pCR-X8-HBc-CETP encoding a B-cell epitope of cholesteryl ester transfer protein (CETP) C-terminal fragment (CETPC) displayed by Hepatitis B virus core (HBc) particle. This plasmid also contained immunostimulatory sequences (ISS) which included eight CpG motifs 5'-GACGTT-3, functioning as immunomodulators. After anti-CETP antibodies were successfully produced, rabbits were fed with a high-cholesterol diet for 15 weeks, and then the antiatherogenic effects of this DNA immunization were evaluated. The results showed that the fraction of plasma cholesterol in HDL significantly increased and the fraction of plasma cholesterol in LDL decreased in the pCR-X8-HBc-CETP immunized rabbits compared with those in the saline control group and one group treated with the plasmid pCR-X8-HBc containing ISS but lacking CETP epitope. More importantly, DNA immunization with pCR-X8-HBe-CETP markedly reduced the average percentage of aortic lesions in the entire aorta area by 80.60% compared with the saline control (3.78% versus 19.48%) and the average thickness of hyperplastic coronary artery in this group was also significantly less than in the saline control group (146 +/- 11 mu m versus 248 18 Vm). Our data also showed that CpG DNA alone could be antiatherogenic in this model because the average percentage of aortic lesions in pCR-X8-HBc immunized rabbits was 16.53% lower than that of the saline control group and the average thickness of hyperplastic coronary artery was also substantially lower than saline control group (155 +/- 13 mu m versus 248 +/- 18 mu m). Thus, plasmid pCR-X8-HBc-CETP could significantly inhibit the progression of atherosclerosis and be potentially developed as a suitable DNA vaccine against atherosclerosis. (c) 2006 Elsevier Ltd. All rights reserved.