Gaofu Qi, Jun Long, Xiuyun Zhao, Wentao Liu, Jie Wu, Jingjing Liu
Center of Enzyme Engineering, Biopharmaceutical College, China Pharmaceutical University, Tongjiaxiang 24, Nanjing 210009 Jiangsu, People's Republic of China.
Life Sci. 2005 Oct 7;77(21):2690-702. doi: 10.1016/j.lfs.2005.05.037.
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.
由天冬酰胺酶、破伤风毒素辅助性T细胞表位和胆固醇酯转运蛋白(CETP)B细胞表位组成的重组嵌合酶AnsB-TTP-CETPC,在明矾佐剂中用于给新西兰白兔接种疫苗。成功产生抗CETP抗体后,给兔子喂食高胆固醇饮食15周,直至动脉中形成动脉粥样硬化病变。结果显示,在rAnsB-TTP-CETPC免疫的兔子中,抗CETP抗体抑制CETP后,高密度脂蛋白(HDL)中的血浆胆固醇比例增加,低密度脂蛋白(LDL)中的血浆胆固醇比例降低。用rAnsB-TTP-CETPC处理的兔子的主动脉粥样硬化斑块平均大小比用卵清蛋白(OVA,中性对照)处理的兔子小42.3%,比用重组热休克蛋白65(rHSP 65,阴性对照)处理的兔子小47.6%。rAnsB-TTP-CETPC免疫的兔子的增生性冠状动脉平均厚度为159±12微米,显著低于rHSP 65免疫的兔子(187±15微米)或OVA免疫的兔子(248±18微米)。此处报告的数据表明,rAnsB-TTP-CETPC可显著减轻喂食高胆固醇饮食的兔子的动脉粥样硬化发展,未来可能开发成为一种抗动脉粥样硬化疫苗。