LDL and apoB
A high-dose tetanus toxoid-CETP vaccine lowers CETP activity and raises HDL-C in rabbits but fails to reduce atherosclerotic lesions (Biomed Pharmacother 2016)
Original title: Anti-atherosclerosis effect of different doses of CETP vaccine in rabbit model of atherosclerosis
Testing three doses (10, 50, and 100 micrograms per rabbit, termed FA10, FA50, FA100) of a Tetanus toxoid-CETP peptide vaccine in a rabbit model of atherosclerosis fed a 2% cholesterol diet, researchers found all doses generated a strong anti-CETP antibody response. Only the highest dose, FA100, significantly reduced CETP activity (P=0.031) and significantly increased HDL-C compared with controls (P=0.006). Despite this successful CETP inhibition and HDL-C elevation, no significant reduction in aortic atherosclerotic lesion development was observed compared with controls, leading the authors to conclude the vaccine's biochemical effects did not translate into atheroprotection and to question whether CETP is an attractive therapeutic target for cardiovascular disease prevention.
Original abstract
Aim: To evaluate atheroprotective effects of different doses of cholesteryl ester transfer protein (CETP) vaccine, three doses of Tetanus toxoid-CETP (TT-CETP) peptide including 10, 50 and 100/rabbit, termed FA10, FA50, FA100, respectively, were administered in rabbit model of atherosclerosis.
Methods: Animals were vaccinated subcutaneously (S.C.) with 100μl of vaccine in presence of complete Freund's adjuvant (CFA) for the first administration. Rabbits were boosted 4 times at 3 weeks intervals with the same peptide dose formulated in incomplete Freund's adjuvant (IFA). Animals were fed with diet supplemented with 2% cholesterol from week 11 to week 19. Anti-TT-CETP specific antibody and CETP activity in sera were determined. Therapeutic response was examined by tracking plasma lipoprotein levels (HDL-C, LDL-C and total cholesterol), and pathologic observation of intima/media thickness at the site of aortic lesions.
Results: All TT-CETP vaccine doses generated strong anti TT-CETP antibody response. CETP activity reduced in rabbits vaccinated with FA100 (P=0.031). FA100 showed significant increase in level of HDL-C rather than control group (P=0.006). However, no significant reduction were found in atherosclerotic lesion when compared to control.
Conclusion: Inhibition of CETP activity and increased HDL-C were found with FA100, but the vaccine failed to prevent aortic lesion development in immunized rabbits when compared to control. Our result supports the hypothesis stated that CETP may not be an attractive therapeutic target for the prevention of cardiovascular disease.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 19 August 2026. Methods.