Antibody against cholesteryl ester transfer protein (CETP) elicited by a recombinant chimeric enzyme vaccine attenuated atherosclerosis in a rabbit model.
The recombinant chimeric enzyme of AnsB-TTP-CETPC, which comprised asparagianse, tetanus toxin helper T-cell epitope and CETP B-cell epitope, was used to vaccinate New Zealand white rabbits in alum adjuvant. After anti-CETP antibodies were successfully produced, rabbits were fed with a high cholesterol diet for fifteen weeks until atherosclerotic lesions formed in arteries. The results showed that after CETP was inhibited by anti-CETP antibodies the fraction of plasma cholesterol in HDL increased and the fraction of plasma cholesterol in LDL decreased in rAnsB-TTP-CETPC immunized rabbits. The average size of aorta atherosclerotic plaques in rabbits treated with rAnsB-TTP-CETPC was 42.3% less than in rabbits treated with OVA (neutral control), or 47.6% less than in rabbits treated with rHSP 65 (negative control). The average thickness of hyperplastic coronary artery in rAnsB-TTP-CETPC immunized rabbits was 159+/-12 microm, which was significantly lower than in rHSP 65 immunized rabbits (187+/-15 microm) or OVA immunized rabbits (248+/-18 microm). The data reported here demonstrated that rAnsB-TTP-CETPC could significantly attenuate the development of atherosclerosis in rabbits fed with high cholesterol diet, and might be developed to an anti-atherosclerosis vaccine in the future.
Gaofu
Qi
Q
Center of Enzyme Engineering, Biopharmaceutical College, China Pharmaceutical University, Tongjiaxiang 24, Nanjing 210009 Jiangsu, People's Republic of China.
Jun
Long
L
Xiuyun
Zhao
Z
Wentao
Liu
L
Jie
Wu
W
Jingjing
Liu
L
D000818:Animals; D019138:Antibodies, Blocking / Q000096:biosynthesis* / Q000627:therapeutic use*; D001161:Arteriosclerosis / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D015153:Blotting, Western; D002352:Carrier Proteins / Q000037:antagonists & inhibitors* / Q000276:immunology*; D053480:Cholesterol Ester Transfer Proteins; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D003331:Coronary Vessels / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006023:Glycoproteins / Q000037:antagonists & inhibitors* / Q000276:immunology*; D006801:Humans; D007668:Kidney / Q000473:pathology; D011817:Rabbits; D011993:Recombinant Fusion Proteins / Q000276:immunology*; D014613:Vaccines, Attenuated; D014614:Vaccines, Synthetic
D019138:Antibodies, Blocking; C506642:CETP protein, human; D002352:Carrier Proteins; D053480:Cholesterol Ester Transfer Proteins; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D006023:Glycoproteins; D011993:Recombinant Fusion Proteins; D014613:Vaccines, Attenuated; D014614:Vaccines, Synthetic