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巨型病毒:一种新型疫苗,可在体内诱导乙肝病毒特异性细胞毒性T淋巴细胞反应。

Mimovirus: a novel form of vaccine that induces hepatitis B virus-specific cytotoxic T-lymphocyte responses in vivo.

作者信息

Wu Yu-Zhang, Zhao Jian-Ping, Wan Ying, Jia Zheng-Cai, Zhou Wei, Bian Jiang, Ni Bing, Zou Li-Yun, Tang Yan

机构信息

Institute of Immunology, Third Military Medical University, Ave. Gaotanyan 30th, District Shapingba, Chongqing 400038, People's Republic of China.

出版信息

J Virol. 2002 Oct;76(20):10264-9. doi: 10.1128/jvi.76.20.10264-10269.2002.

Abstract

CD8(+) cytotoxic T lymphocytes (CTLs) are now recognized as important mediators of immunity against intracellular pathogens, including human immunodeficiency virus and tumors. How to efficiently evoke antigen-specific CTL responses in vivo has become a crucial problem in the development of modern vaccines. Here, we developed a completely novel CTL vaccine-mimovirus, which is a kind of virus-size particulate antigen delivery system. It was formed by the self-assembly of a cationic peptide containing 18 lysines and a CTL-epitope peptide of HBsAg(28-39), with a plasmid encoding mouse interleukin-12 (IL-12) through electrostatic interactions. We examined the formation of mimovirus by DNA retardation assay, DNase I protection assay, and transmission electron microscopy and demonstrated that mimovirus could efficiently transfer the plasmid encoding IL-12 into mammalian cells such as P815 cells in vitro. Furthermore, it was proved that mimovirus could induce an HBsAg(28-39)-specific CTL response in vivo. Considering its effectiveness, flexibility, and defined composition, mimovirus is potentially a novel system for vaccination against intracellular pathogens and tumors.

摘要

CD8(+) 细胞毒性T淋巴细胞(CTLs)如今被认为是针对包括人类免疫缺陷病毒和肿瘤在内的细胞内病原体的重要免疫介质。如何在体内有效激发抗原特异性CTL反应已成为现代疫苗开发中的关键问题。在此,我们开发了一种全新的CTL疫苗——拟病毒,它是一种病毒大小的颗粒抗原递送系统。它由含18个赖氨酸的阳离子肽与乙肝表面抗原(HBsAg)(28 - 39)的CTL表位肽通过静电相互作用自组装而成,并与编码小鼠白细胞介素-12(IL - 12)的质粒结合。我们通过DNA阻滞试验、DNase I保护试验和透射电子显微镜检查了拟病毒的形成,并证明拟病毒能够在体外将编码IL - 12的质粒有效转移至哺乳动物细胞如P815细胞中。此外,还证明了拟病毒能够在体内诱导HBsAg(28 - 39)特异性CTL反应。鉴于其有效性、灵活性和明确的组成,拟病毒可能是一种针对细胞内病原体和肿瘤进行疫苗接种的新型系统。

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