2013-01-012024-05-14https://scholars.lib.ntu.edu.tw/handle/123456789/658311摘要：此計畫中提到，我們已開發了一種製備膽固醇酯轉移蛋白(CETP)之胜肽疫苗的平台，這種膽固醇酯轉移蛋白的疫苗是由群集的膽固醇酯轉移蛋白抗原決定位(epitope)，連接著免疫球蛋白的Fc 功能區所構成。Fc-tagged 的胜肽疫苗可被抗原呈現細胞經由Fc 接受器攝入，而且可以增加抗原的半生期以及在不添加佐劑時增加免疫原特性。我們的初步成果顯示CETP 的疫苗可以誘發高效價的CETP 抗體、可以降低CETP 活性，而且可以阻斷餵食高膽固醇飼料兔子的動脈硬化。此外，在疫苗安全性評估上，經由病理醫師在病理學的診斷發現，在接受疫苗的兔子腎臟中初步並未發現明顯病變。因此CETP 疫苗具有阻斷動脈硬化發展的潛力。本計畫的目標在於開發免添加佐劑之Fc- tagged CETP 疫苗以及人用的CETP 單株抗體用於治療動脈粥狀硬化。本計畫的研究目標1: 評估疫苗在不添加佐劑時的有效性。在施打疫苗的實驗組兔子中，比較添加佐劑與否，對於產生的CETP 抗體效價以及對CETP 活性的影響。研究目標2:探討Fc- tagged CETP 疫苗對於總膽固醇濃度(Total cholesterol)、低密度脂蛋白(LDL-C)濃度、高密度脂蛋白濃度(HDL-C)、ApoA1 濃度以及動脈硬化的發展等之影響。研究目標3:製備人用之CETP 單株抗體以及人用CETP 疫苗供將來臨床研究使用。<br> Abstract: Low level of HDL-cholesterol (HDL-C) is well recognized as an independent risk factor for cardiovascular disease. Cholesterol ester transfer protein (CETP) is a key mediator of reverse cholesterol transport, and inhibition of CETP is able to raise HDL-C. In this proposal, we develop a platform for novel anti-CETP peptide vaccine which contains a clustering epitope of CETP tagged with the immunoglobulin Fc domain. Fc-tagged vaccine can be uptaken by antigen-presenting cells mediated by Fc receptor and be prolonged half-lives and immunogenic in the absence of adjuvant. Our preliminary results showed anti-CETP vaccine could elicit high titer of specific antibody to neutralize CETP activity and to block atherosclerosis in rabbits fed high-fat diet. Furthermore, pathological examinations showed no evidence of pathological changes in kidney of the vaccinated rabbits, suggesting that anti-CETP vaccine has potential to prevent the progression of atherosclerosis. The goal of this roposal is to develop an adjuvant free Fc-tagged anti-CETP vaccine and humanized anti-CETP antibody for the treatment of atherosclerosis. The specific aim 1: Evaluate the efficacy of anti-CETP vaccine in the absence or presence of adjuvant. The titer of anti-CETP antibody and CETP activity will be compared in rabbits immunized with anti-CETP vaccine in the absence or presence of adjuvant. Aim2: Examine the effect of anti-CETP vaccine on the plasma concentrations of total-C, LDL-C, HDL-C and ApoA1, and the progression of atherosclerosis. Aim3: Generate humanize monoclonal anti-CETP antibody and humanized anti-CETP vaccine for clinical study.動脈粥狀硬化膽固醇脂轉移蛋白疫苗高密度脂蛋白心血管疾病膽固醇非酒精性脂肪肝atherosclerosisCETPvaccineHDLCardiovascular Diseasecholesterolnon-alcoholic fatty liver