Daemen Toos, de Mare Arjan, Bungener Laura, de Jonge Jørgen, Huckriede Anke, Wilschut Jan
Department of Medical Microbiology, Molecular Virology Section, University of Groningen, Anthonius Deusinglaan 1, 9713 AV Groningen, The Netherlands.
Adv Drug Deliv Rev. 2005 Jan 10;57(3):451-63. doi: 10.1016/j.addr.2004.09.005.
Specific targeting and delivery as well as the display of antigens on the surface of professional antigen-presenting cells (APCs) are key issues in the design and development of new-generation vaccines aimed at the induction of both humoral and cell-mediated immunity. Prophylactic vaccination against infectious diseases in general aims at the induction of humoral immune responses to prevent infection. This humoral immune response is mediated by antibody-producing B cells. On the other hand, therapeutic immunisation against virally infected cells and tumour cells requires the induction of cytotoxic T lymphocytes (CTLs) that can specifically recognise and lyse infected cells or transformed tumour cells. The induction of Major Histocompatibility Complex (MHC) class I restricted CTL activity is optimally achieved by synthesis of antigens within APCs, for example, after immunisation with live attenuated virus. However, immunisation with live vaccines bears the risk of causing disease. Therefore, alternative vaccine delivery systems, which enable introduction of nonreplicating antigen into the MHC class I presentation pathway, are sought. Furthermore, for the induction of effective humoral and cellular responses, MHC class II restricted activation of T helper cells (Th cells) is required. Among other delivery systems, as described in this theme issue of Advanced Drug Delivery Reviews, virosomes seem ideally suited for delivery of antigens into both MHC pathways. In this review, we will focus on the use of virosomes as carrier vehicles for the intracellular delivery of protein antigens and DNA, and the induction of a cellular immune response against encapsulated protein antigens and proteins expressed by virosome-associated plasmids.
特异性靶向与递送以及抗原在专职抗原呈递细胞（APC）表面的展示，是旨在诱导体液免疫和细胞介导免疫的新一代疫苗设计与开发中的关键问题。一般来说，针对传染病的预防性疫苗接种旨在诱导体液免疫反应以预防感染。这种体液免疫反应由产生抗体的B细胞介导。另一方面，针对病毒感染细胞和肿瘤细胞的治疗性免疫需要诱导细胞毒性T淋巴细胞（CTL），其能够特异性识别并裂解感染细胞或转化的肿瘤细胞。通过在APC内合成抗原，例如在用减毒活病毒免疫后，可最佳地诱导主要组织相容性复合体（MHC）I类限制性CTL活性。然而，使用活疫苗进行免疫存在引发疾病的风险。因此，人们正在寻找能够将非复制性抗原引入MHC I类呈递途径的替代疫苗递送系统。此外，为了诱导有效的体液和细胞反应，需要MHC II类限制性激活辅助性T细胞（Th细胞）。在本《高级药物递送评论》主题特刊中描述的其他递送系统中，病毒体似乎非常适合将抗原递送至两种MHC途径。在这篇综述中，我们将重点关注病毒体作为载体用于蛋白质抗原和DNA的细胞内递送，以及诱导针对包封的蛋白质抗原和病毒体相关质粒表达的蛋白质的细胞免疫反应。
