Luong Michael, Lam Jennifer S, Chen Jianmin, Levitz Stuart M
Department of Microbiology and Immunology Training Program, Boston University School of Medicine, Boston, MA 02118, USA.
Vaccine. 2007 May 30;25(22):4340-4. doi: 10.1016/j.vaccine.2007.03.027. Epub 2007 Mar 30.
Targeting dendritic cell mannose receptors by mannosylating antigens represents a promising vaccination strategy. Using the model antigen ovalbumin (OVA) expressed recombinantly in bacterial and yeast vectors, we have previously demonstrated fungal mannosylation enhances antigen immunogenicity in the context of CD4(+) T cell responses. However, because protection against many tumors and pathogens is thought to require MHC class I-restricted T cell responses, the capacity of differentially mannosylated OVA antigens to induce antigen-specific CD8(+) T cell proliferation was determined. We found that mannosylated yeast-derived OVA antigens were more potent than their unmannosylated counterparts at inducing antigen-specific T cell proliferation. However, the type of mannosylation was critical as addition of extensive O-linked mannosylation increased lymphoproliferative responses while the presence of N-linked mannosylation was associated with decreased responses. Mannosylated OVA failed to stimulate TNF-alpha and IL-12 production from dendritic cells. These data suggest that vaccines incorporating mannosylation must take into account how the mannose groups are linked to the core antigen and may need to include an adjuvant to stimulate cytokine production.
通过对抗原进行甘露糖化修饰来靶向树突状细胞甘露糖受体是一种很有前景的疫苗接种策略。利用在细菌和酵母载体中重组表达的模型抗原卵清蛋白（OVA），我们之前已经证明，在CD4(+) T细胞应答的背景下，真菌甘露糖化修饰可增强抗原的免疫原性。然而，由于人们认为针对许多肿瘤和病原体的保护需要MHC I类限制性T细胞应答，因此我们测定了不同甘露糖化修饰的OVA抗原诱导抗原特异性CD8(+) T细胞增殖的能力。我们发现，甘露糖化修饰的酵母来源的OVA抗原在诱导抗原特异性T细胞增殖方面比未修饰的对应物更有效。然而，甘露糖化修饰的类型至关重要，因为添加广泛的O-连接甘露糖会增加淋巴细胞增殖反应，而N-连接甘露糖的存在则与反应降低有关。甘露糖化修饰的OVA未能刺激树突状细胞产生TNF-α和IL-12。这些数据表明，包含甘露糖化修饰的疫苗必须考虑甘露糖基团与核心抗原的连接方式，并且可能需要包含佐剂来刺激细胞因子的产生。
