Bungener Laura, Huckriede Anke, Wilschut Jan, Daemen Toos
Department of Medical Microbiology, University of Groningen, The Netherlands.
Biosci Rep. 2002 Apr;22(2):323-38. doi: 10.1023/a:1020198908574.
The induction of effective cellular and humoral immune responses against protein antigens is of major importance in vaccination strategies against infectious diseases and cancer. Immunization with protein alone in general does not result in efficient induction of cytotoxic T lymphocyte (CTL) and antibody responses. Numerous other immunization strategies have been explored. In this review we will discuss a number of lipid-based antigen delivery systems suitable for the induction of CTL responses. These systems comprise reconstituted virus envelopes (virosomes), liposomes, and immune-stimulating complexes (ISCOMs). We will concentrate on delivery of the protein antigen ovalbumin (OVA) since extensive studies with this antigen have been performed for all of the systems discussed, allowing direct comparison of antigen delivery efficiency. Stimulation of CTL activity requires processing of the antigen in the cytosol of antigen-presenting cells (APCs) and presentation of antigenic peptides on surface major histocompatibility class I complexes (MHC class I). In vitro, the ability of antigen delivery systems to induce MHC class I presentation indeed correlates with their capacity to deliver antigen to the cytosol of cells. This capacity appears to be less important for the induction of cytotoxic T lymphocytes in vivo. Instead, other properties of the antigen delivery system like activation of APCs and induction of T helper cells play a more prominent role. Fusion-active virosomes appear to be a very potent system for induction of CTL activity, most likely since virosomes combine efficient delivery of antigen with general stimulation of the immune system.
诱导针对蛋白质抗原的有效细胞免疫和体液免疫反应在针对传染病和癌症的疫苗接种策略中至关重要。一般来说，单独用蛋白质进行免疫接种不会有效诱导细胞毒性T淋巴细胞（CTL）和抗体反应。人们已经探索了许多其他免疫接种策略。在这篇综述中，我们将讨论一些适合诱导CTL反应的基于脂质的抗原递送系统。这些系统包括重组病毒包膜（病毒体）、脂质体和免疫刺激复合物（ISCOM）。我们将重点讨论蛋白质抗原卵清蛋白（OVA）的递送，因为针对所有所讨论的系统都对该抗原进行了广泛研究，从而能够直接比较抗原递送效率。刺激CTL活性需要抗原呈递细胞（APC）的胞质溶胶中对抗原进行加工，并在表面主要组织相容性复合体I类（MHC I类）上呈递抗原肽。在体外，抗原递送系统诱导MHC I类呈递的能力确实与其将抗原递送至细胞胞质溶胶的能力相关。这种能力在体内诱导细胞毒性T淋巴细胞方面似乎不太重要。相反，抗原递送系统的其他特性，如APC的激活和辅助性T细胞的诱导，发挥着更突出的作用。具有融合活性的病毒体似乎是诱导CTL活性的非常有效的系统，这很可能是因为病毒体将抗原的有效递送与免疫系统的一般刺激结合在一起。
