Sheng Kuo-Ching, Kalkanidis Martha, Pouniotis Dodie S, Esparon Sandra, Tang Choon Kit, Apostolopoulos Vasso, Pietersz Geoffrey A
Immunology and Vaccine Laboratory, Burnet Institute, Melbourne, Australia.
Eur J Immunol. 2008 Feb;38(2):424-36. doi: 10.1002/eji.200737578.
Antigen mannosylation has been shown to be an effective approach to potentiate antigen immunogenicity, due to the enhanced antigen uptake and presentation by APC. To overcome disadvantages associated with conventional methods used to mannosylate antigens, we have developed a novel mannose-based antigen delivery system that utilizes a polyamidoamine (PAMAM) dendrimer. It is demonstrated that mannosylated dendrimer ovalbumin (MDO) is a potent immune inducer. With a strong binding avidity to DC, MDO potently induced OVA-specific T cell response in vitro. It was found that the immunogenicity of MDO was due not only to enhanced antigen presentation, but also to induction of DC maturation. Mice immunized with MDO generated strong OVA-specific CD4(+)/CD8(+) T cell and antibody responses. MDO also targeted lymph node DC to cross-present OVA, leading to OTI CD8(+) T cell proliferation. Moreover, upon challenge with B16-OVA tumor cells, tumors in mice pre-immunized with MDO either did not grow or displayed a much more delayed onset, and had slower kinetics of growth than those of OVA-immunized mice. This mannose-based antigen delivery system was applied here for the first time to the immunization study. With several advantages and exceptional adjuvanticity, we propose mannosylated dendrimer as a potential vaccine carrier.
由于抗原呈递细胞（APC）增强了对抗原的摄取和呈递，抗原甘露糖化已被证明是增强抗原免疫原性的有效方法。为了克服与用于抗原甘露糖化的传统方法相关的缺点，我们开发了一种新型的基于甘露糖的抗原递送系统，该系统利用聚酰胺胺（PAMAM）树枝状大分子。结果表明，甘露糖化树枝状大分子卵清蛋白（MDO）是一种有效的免疫诱导剂。MDO对树突状细胞（DC）具有很强的结合亲和力，在体外能有效诱导OVA特异性T细胞反应。研究发现，MDO的免疫原性不仅归因于增强的抗原呈递，还归因于DC成熟的诱导。用MDO免疫的小鼠产生了强烈的OVA特异性CD4(+)/CD8(+) T细胞和抗体反应。MDO还靶向淋巴结DC以交叉呈递OVA，导致OTI CD8(+) T细胞增殖。此外，在用B16-OVA肿瘤细胞攻击后，预先用MDO免疫的小鼠中的肿瘤要么不生长，要么显示出更延迟的发病，并且与用OVA免疫的小鼠相比，其生长动力学更慢。这种基于甘露糖的抗原递送系统首次应用于免疫研究。由于具有多种优点和出色的佐剂活性，我们提出甘露糖化树枝状大分子作为一种潜在的疫苗载体。
