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重组细小病毒样颗粒作为抗原载体:一种引发保护性抗病毒细胞毒性T细胞的新型非复制性外源抗原。

Recombinant parvovirus-like particles as an antigen carrier: a novel nonreplicative exogenous antigen to elicit protective antiviral cytotoxic T cells.

作者信息

Sedlik C, Saron M, Sarraseca J, Casal I, Leclerc C

机构信息

Unité de Biologie des Régulations Immunitaires, Institut Pasteur, 25 rue du Docteur Roux, 75724 Paris cedex 15, France.

出版信息

Proc Natl Acad Sci U S A. 1997 Jul 8;94(14):7503-8. doi: 10.1073/pnas.94.14.7503.

Abstract

To develop a strategy that promotes efficient antiviral immunity, hybrid virus-like particles (VLP) were prepared by self-assembly of the modified porcine parvovirus VP2 capsid protein carrying a CD8(+) T cell epitope from the lymphocytic choriomeningitis virus nucleoprotein. Immunization of mice with these hybrid pseudoparticles, without adjuvant, induced strong cytotoxic T lymphocyte (CTL) responses against both peptide-coated- or virus-infected-target cells. This CD8(+) class I-restricted cytotoxic activity persisted in vivo for at least 9 months. Furthermore, the hybrid parvovirus-like particles were able to induce a complete protection of mice against a lethal lymphocytic choriomeningitis virus infection. To our knowledge, this study represents the first demonstration that hybrid nonreplicative VLP carrying a single viral CTL epitope can induce protection against a viral lethal challenge, in the absence of any adjuvant. These recombinant particles containing a single type of protein are easily produced by the baculovirus expression system and, therefore, represent a promising and safe strategy to induce strong CTL responses for the elimination of virus-infected cells.

摘要

为制定一种促进高效抗病毒免疫的策略,通过自组装携带来自淋巴细胞性脉络丛脑膜炎病毒核蛋白的CD8(+) T细胞表位的修饰猪细小病毒VP2衣壳蛋白,制备了杂交病毒样颗粒(VLP)。用这些杂交假颗粒免疫小鼠,无需佐剂,即可诱导针对肽包被靶细胞或病毒感染靶细胞的强烈细胞毒性T淋巴细胞(CTL)反应。这种CD8(+) I类限制性细胞毒性活性在体内持续至少9个月。此外,杂交细小病毒样颗粒能够诱导小鼠完全抵抗致死性淋巴细胞性脉络丛脑膜炎病毒感染。据我们所知,本研究首次证明携带单一病毒CTL表位的杂交非复制性VLP在无任何佐剂的情况下可诱导抵抗病毒致死性攻击的保护作用。这些含有单一类型蛋白质的重组颗粒可通过杆状病毒表达系统轻松生产,因此是诱导强烈CTL反应以消除病毒感染细胞的一种有前景且安全的策略。

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