Immunogenic Comparison of Chimeric Adenovirus 5/35 Vector Carrying Optimized Human Immunodeficiency Virus Clade C Genes and Various Promoters
Immunogenic Comparison of Chimeric Adenovirus 5/35 Vector Carrying Optimized Human Immunodeficiency Virus Clade C Genes and Various Promoters
复制标题
携带优化的人类免疫缺陷病毒进化枝C基因和各种启动子的嵌合腺病毒5/35载体的免疫原性比较
作者：
Masaki Shoji;Shinji Yoshizaki;H. Mizuguchi;K. Okuda;M. Shimada
腺病毒载体疫苗是一种很有前途的预防HIV感染的方法。然而，最近使用该载体的IIb期临床试验并未显示其对艾滋病毒感染的保护效果。为了改进疫苗，我们通过优化密码子的使用、启动子和接合子来探索转基因蛋白的表达及其免疫原性。我们比较了不同启动子(CMV、CMVi和CA启动子)和适配器(IRES和F2A)驱动的携带天然或密码子使用优化的HIV-1分支C Gag和env基因表达盒的腺病毒载体疫苗的蛋白表达和免疫原性。含有优化的Gag基因的腺病毒载体疫苗在小鼠体内产生了比含有天然Gag基因的载体更高的Gag蛋白表达和更高的免疫应答。此外，CA启动子比其他两种常用的启动子(CMV和CMVi)产生更高的转基因表达和更高的免疫应答。与IRES和直接融合蛋白相比，使用F2a接头的第二次基因表达具有更高的蛋白表达和免疫力。综上所述，含有CA启动子的表达框、优化的HIV-1分支C基因和F2a接头的腺病毒载体获得了最好的蛋白表达，并诱导了最高的转基因特异性免疫应答。这一发现将为疫苗设计和基因治疗带来希望。
Adenovirus vector-based vaccine is a promising approach to protect HIV infection. However, a recent phase IIb clinical trial using the vector did not show its protective efficacy against HIV infection. To improve the vaccine, we explored the transgene protein expression and its immunogenicity using optimized codon usage, promoters and adaptors. We compared protein expression and immunogenicity of adenovirus vector vaccines carrying native or codon usage-optimized HIV-1 clade C gag and env genes expression cassettes driven by different promoters (CMV, CMVi, and CA promoters) and adapters (IRES and F2A). The adenovirus vector vaccine containing optimized gag gene produced higher Gag protein expression and induced higher immune responses than the vector containing native gag gene in mice. Furthermore, CA promoter generated higher transgene expression and elicited higher immune responses than other two popularly used promoters (CMV and CMVi). The second gene expression using F2A adaptor resulted in higher protein expression and immunity than that of using IRES and direct fusion protein. Taken together, the adenovirus vector containing the expression cassette with CA promoter, optimized HIV-1 clade C gene and an F2A adaptor produced the best protein expression and elicited the highest transgene-specific immune responses. This finding would be promising for vaccine design and gene therapy.
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影响因子：
20.3
作者：
Betts, Michael R.;Nason, Martha C.;Koup, Richard A.
通讯作者：
Koup, Richard A.
酶联免疫斑点、细胞因子流式细胞术和四聚体用于检测黑色素瘤患者对树突状细胞多肽疫苗的 T 细胞反应。
DOI：
--
发表时间：
2003
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Whiteside,TheresaL;Zhao,Yongxiang;Tsukishiro,Takashi;Elder,ElaineM;Gooding,William;Baar,Joseph
通讯作者：
Baar,Joseph
直接检测细胞对癌症疫苗的免疫反应。
DOI：
10.1067/msy.2001.108609
发表时间：
2001
期刊：
Surgery.
影响因子：
--
作者：
Mosca,PJ;Hobeika,AC;Clay,TM;Morse,MA;Lyerly,HK
通讯作者：
Lyerly,HK
影响因子：
4.2
作者：
Mizuguchi, H;Kay, MA
通讯作者：
Kay, MA