Virosome-mediated delivery of protein antigens in vivo: efficient induction of class I MHC-restricted cytotoxic T lymphocyte activity
Virosome-mediated delivery of protein antigens in vivo: efficient induction of class I MHC-restricted cytotoxic T lymphocyte activity
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DOI：
10.1016/j.vaccine.2004.09.002
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发表时间：
2005-01-26
期刊：
影响因子：
5.5
通讯作者：
Daemen, T
中科院分区：
文献类型：
--
作者：
Bungener, L;Huckriede, A;Daemen, T
诱导针对蛋白抗原的CTL反应是疫苗开发的重要目标。在本文中，我们提出融合活性病毒体作为一种疫苗递送系统，能够有效地诱导体内CTL反应。病毒体是重组的病毒膜，它不包含它们来源于的病毒的遗传物质。在重组过程中，包括蛋白抗原在内的外源大分子可以被包裹在病毒体中。功能重组的病毒体保留了原生病毒的细胞结合和融合特性。因此，在通过受体介导的内吞作用被细胞摄取后，病毒体将其内容物递送到细胞质中。在之前的一项研究中，我们证明了以这种方式递送到树突状细胞的蛋白抗原在MHC I类和11类呈递中都得到了有效的处理。在此，我们研究了在小鼠体内诱导针对病毒体包封的卵清蛋白（OVA）的细胞免疫应答。通过融合活性病毒体传递的0.75 μ g卵细胞就足以诱导强大的I类mhc限制性CTL反应。采用的所有免疫途径（i.m.、i.p.和s.c）均能有效诱导CTL活性。在标准cr -51释放试验中，诱导的ctl具有细胞毒性，并产生ifn - γ作为对OVA肽的反应。因此，病毒体代表了一种理想的抗原递送系统，用于诱导细胞免疫对抗包裹蛋白抗原。(C) 2004 Elsevier Ltd.版权所有。
Induction of CTL responses against protein antigens is an important aim in vaccine development. In this paper we present fusion-active virosomes as a vaccine delivery system capable of efficient induction of CTL responses in vivo. Virosomes are reconstituted viral membranes, which do not contain the genetic material of the virus they are derived from. Foreign macromolecules, including protein antigens, can be encapsulated in virosomes during the reconstitution process. Functionally reconstituted virosomes retain the cell binding and fusion characteristics of the native virus. Thus, upon uptake by cells through receptor-mediated endocytosis, virosomes will deliver their content to the cell cytosol. In a previous study, we demonstrated that protein antigens delivered in this manner to dendritic cells are efficiently processed for both MHC class I and class 11 presentation. Here, we studied in vivo induction of cellular immune responses against virosome-encapsulated ovalbumin (OVA) in mice. As little as 0.75 mug OVA delivered by fusion-active virosomes was sufficient to induce a powerful class I MHC-restricted CTL response. All immunization routes that were used (i.m., i.p. and s.c.) resulted in efficient induction of CTL activity. The CTLs induced were cytotoxic in a standard Cr-51-release assay and produced IFN-gamma in response to OVA peptide. Thus, virosomes represent an ideal antigen delivery system for induction of cellular immunity against encapsulated protein antigens. (C) 2004 Elsevier Ltd. All rights reserved.