Enhancement of suicidal DNA vaccine potency by linking Mycobacterium tuberculosis heat shock protein 70 to an antigen
Enhancement of suicidal DNA vaccine potency by linking Mycobacterium tuberculosis heat shock protein 70 to an antigen
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DOI：
10.1038/sj.gt.3301408
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发表时间：
2001-03-01
期刊：
影响因子：
5.1
通讯作者：
Wu, TC
中科院分区：
文献类型：
--
作者：
Hsu, KF;Hung, CF;Wu, TC
裸 DNA 疫苗因其稳定性和递送简单性而成为产生抗原特异性免疫的一种有吸引力的方法。然而，DNA 疫苗存在一些特别的问题，例如可能整合到宿主基因组中、细胞转化和有限的效力。基于 DNA 的甲病毒 RNA 复制子（自杀性 DNA 载体）的使用可以减轻整合或转化的担忧，因为自杀性 DNA 载体最终会导致转染细胞裂解。为了进一步提高自杀性 DNA 疫苗的效力，我们评估了将结核分枝杆菌热休克蛋白 70 (Hsp70) 与人乳头瘤病毒 16 型 (HPV-16) E7 连接作为模型抗原对基于 DNA 的塞姆利基森林病毒 (SFV) RNA 载体 pSCA1 产生的抗原特异性免疫的影响。我们的结果表明，与含有野生型 E7 基因的疫苗相比，这种含有 E7/Hsp70 融合基因的自杀性 DNA 疫苗在接种小鼠中产生了明显更高的 E7 特异性 T 细胞介导的免疫反应。更重要的是，这种融合将一种效果较差的疫苗转变为一种对已表达 E7 的转移性肿瘤具有显着效力的疫苗。抗肿瘤作用主要依赖于CD8。这些结果表明Hsp70与抗原的连接可以极大地增强自杀DNA疫苗的效力。
Naked DNA vaccines represent an attractive approach for generating antigen-specific immunity because of their stability and simplicity of delivery. There are particular concerns with DNA vaccines however, such as potential integration into the host genome, cell transformation, and limited potency The usage of DNA-based alphaviral RNA replicons (suicidal DNA vectors) may alleviate the concerns of integration or transformation since suicidal DNA vectors eventually cause lysis of transfected cells. To improve further the potency of suicidal DNA vaccines, we evaluated the effect of linking Mycobacterium tuberculosis heat shock protein 70 (Hsp70) to human papillomavirus type 16 (HPV-16) E7 as a model antigen on antigen-specific immunity generated by a DNA-based Semliki Forest virus (SFV) RNA vector, pSCA1. Our results indicated that this suicidal DNA vaccine containing E7/Hsp70 fusion genes generated significantly higher E7-specific T cell-mediated immune responses than vaccines containing the wild-type E7 gene in vaccinated mice. More importantly, this fusion converted a less effective vaccine into one with significant potency against established E7-expressing metastatic tumors. The antitumor effect was predominantly CD8-dependent. These results indicate that linkage of Hsp70 to the antigen may greatly enhance the potency of suicidal DNA vaccines.