Department of Applied Biochemistry, Tokai University, Hiratsuka, Kanagawa 259-1292, Japan.
Biomed Res Int. 2013;2013:562924. doi: 10.1155/2013/562924. Epub 2013 Oct 10.
Professional phagocytic cells, such as dendritic cells, are mainly responsible for phagocytosis, antigen presentation, and cytokine secretion, which induce subsequent activation of T cell-mediated immunity. Thus, strategies that deliver antigens and stimulatory signals to the cells have significant implications for vaccine design. In this paper, we summarize the potential for liposomes coated with the neoglycolipids containing oligomannose residues (OMLs) as a novel adjuvant for induction of Th1 immune responses and CTLs specific for the encased antigen. OMLs preferentially take up peripheral phagocytic cells. In response to OML uptake, the cells secrete IL-12 selectively, enhance the expression of costimulatory molecules, and migrate into lymphoid tissues from peripheral tissues. OMLs also have the ability to deliver encapsulated protein antigens to the MHC class I and class II pathways to generate antigen-specific CTLs and Th1 cells, respectively, and lipid antigen to CD1d to activate NKT cells. Since administration of OML-based vaccines can eliminate an established tumor, inhibit elevation of the serum IgE level, and prevent progression of protozoan infections in several murine, human, and bovine models, OML-based vaccines have revealed their potential for clinical use in vaccination for a variety of diseases in which CTLs and/or Th1 cells act as effector cells.
专业的吞噬细胞,如树突状细胞,主要负责吞噬、抗原呈递和细胞因子分泌,从而诱导随后的 T 细胞介导的免疫激活。因此,将抗原和刺激信号递送到细胞中的策略对疫苗设计具有重要意义。在本文中,我们总结了含有寡甘露糖残基(OML)的糖脂包被的脂质体作为诱导 Th1 免疫应答和针对包裹抗原的 CTL 的新型佐剂的潜力。OML 优先摄取外周吞噬细胞。在 OML 摄取后,细胞选择性地分泌 IL-12,增强共刺激分子的表达,并从外周组织迁移到淋巴组织。OML 还具有将包裹的蛋白质抗原递送至 MHC Ⅰ类和Ⅱ类途径以分别产生针对抗原的 CTL 和 Th1 细胞,以及将脂质抗原递送至 CD1d 以激活 NKT 细胞的能力。由于基于 OML 的疫苗的给药可以消除已建立的肿瘤、抑制血清 IgE 水平的升高,并预防几种啮齿动物、人类和牛模型中的原生动物感染的进展,因此基于 OML 的疫苗已经显示出它们在用于预防各种疾病的疫苗接种中的临床应用潜力,在这些疾病中 CTL 和/或 Th1 细胞作为效应细胞发挥作用。