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首页> 外文期刊>Vaccine >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
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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

机译：用编码由HBc蛋白显示并含有CpG DNA的26个氨基酸的CETP表位的DNA疫苗进行肌内免疫抑制兔动脉粥样硬化模型中的动脉粥样硬化

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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-HBc-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 microm versus 248+/-18 microm). 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 microm versus 248+/-18 microm). Thus, plasmid pCR-X8-HBc-CETP could significantly inhibit the progression of atherosclerosis and be potentially developed as a suitable DNA vaccine against atherosclerosis.
机译：用质粒pCR-X8-HBc-CETP肌肉内免疫兔，该质粒编码由乙型肝炎病毒核心（HBc）颗粒显示的胆固醇酯转移蛋白（CETP）C端片段（CETPC）的B细胞表位。该质粒还含有免疫刺激序列（ISS），其包括八个CpG基序5'-GACGTT-3'，起免疫调节剂的作用。成功产生抗CETP抗体后，给兔子喂食高胆固醇饮食15周，然后评估这种DNA免疫的抗动脉粥样硬化作用。结果表明，与生理盐水对照组和用质粒pCR-β处理的一组相比，经pCR-X8-HBc-CETP免疫的兔中HDL中的血浆胆固醇分数显着增加，而LDL中的血浆胆固醇分数降低。 X8-HBc包含ISS，但缺少CETP表位。更重要的是，与生理盐水对照组相比，pCR-X8-HBc-CETP的DNA免疫显着降低了整个主动脉区域的平均主动脉病变百分比，降低了80.60％（3.78％对19.48％）和增生性冠状动脉的平均厚度该组也显着低于生理盐水对照组（146 +/- 11微米对248 +/- 18微米）。我们的数据还显示，在此模型中，单独的CpG DNA可能具有抗动脉粥样硬化作用，因为经pCR-X8-HBc免疫的兔子的主动脉病变平均百分率比生理盐水对照组低16.53％，并且增生性冠状动脉的平均厚度也大大低于生理盐水对照组（155 +/- 13微米对248 +/- 18微米）。因此，质粒pCR-X8-HBc-CETP可以显着抑制动脉粥样硬化的发展，并有可能作为抗动脉粥样硬化的合适DNA疫苗而开发。

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