Novel Adenovirus type 5 vaccine platform induces cellular immunity against HIV-1 Gag, Pol, Nef despite the presence of Ad5 immunity
Novel Adenovirus type 5 vaccine platform induces cellular immunity against HIV-1 Gag, Pol, Nef despite the presence of Ad5 immunity
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DOI：
10.1016/j.vaccine.2009.06.028
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发表时间：
2009-01-01
期刊：
影响因子：
5.5
通讯作者：
Jones, Frank R.
中科院分区：
文献类型：
--
作者：
Gabitzsch, Elizabeth S.;Xu, Younong;Jones, Frank R.
重组腺病毒血清型5 （Ad5）载体已在许多动物和人类临床研究中用作疫苗平台。由于预先存在的Ad5免疫，Ad5疫苗诱导的免疫反应可以减轻。我们之前报道了使用一种新的Ad5平台在Ad5超免疫小鼠中诱导针对HIV-1 Gag的细胞免疫反应（CMI）。在这里，使用HIV-1 Gag、Pol和Nef作为抗原转基因的三合一混合物来评估Ad5 [E1-， E2b-]疫苗平台的有效性。用表达HIV-1的载体接种Ad5幼稚和Ad5免疫小鼠后，可诱导广泛CMI。三种疫苗的混合物即使在Ad5高免疫存在的情况下，也能诱导针对每种转基因产物的CMI。这些研究表明，Ad5 [E1-, E2b-]-gag、Ad5 [E1-， E2b-]-pol或Ad5 [E1-， E2b-]-nef载体对CMI的免疫应答具有转基因特异性，不会诱导CMI对无关抗原如癌胚抗原（CEA）、单纯疱疹病毒糖蛋白B （HSV）、巨细胞病毒（CMV）或流感病毒抗原产生应答。我们正在非人类灵长类动物模型中评估这种重组三联体病毒载体作为HIV-1疫苗，数据表明该疫苗值得临床评估。2009爱思唯尔有限公司版权所有。
Recombinant Adenovirus serotype 5 (Ad5) vectors have been used as vaccine platforms in numerous animal and human clinical studies. The immune response induced by Ad5 vaccines can be mitigated due to pre-existing Ad5 immunity. We previously reported the use of a novel Ad5 platform to induce cellular immune responses (CMI) against HIV-1 Gag in Ad5 hyper immune mice. Here, the effectiveness of the Ad5 [E1-, E2b-] vaccine platform was evaluated using a triad mixture of HIV-1 Gag, Pol, and Nef as antigenic transgenes. Broad CMI was induced following vaccination with the HIV-1 expressing vectors in Ad5 naive and Ad5 immunized mice. A mixture of the three vaccines induced CMI against each transgene product even in the presence of hyper Ad5 immunity. These studies revealed that CMI responses to immunization with Ad5 [E1-, E2b-]-gag, Ad5 [E1-, E2b-]-pol or Ad5 [E1-, E2b-]-nef vectors were transgene specific and did not induce CMI responses against irrelevant antigens such as carcinoembryonic antigen (CEA), herpes simplex virus glycoprotein B (HSV), cytomegalovirus (CMV) or influenza virus antigens. We are evaluating this recombinant triad viral vector as an HIV-1 vaccine in a non-human primate model and the data indicate that the vaccine is worthy of clinical evaluation. (C) 2009 Elsevier Ltd. All rights reserved.