M cell-targeted DNA vaccination
M cell-targeted DNA vaccination
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DOI：
10.1073/pnas.161204098
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发表时间：
2001-07-31
影响因子：
11.1
通讯作者：
Pascual, DW
中科院分区：
文献类型：
--
作者：
Wu, YP;Wang, XH;Pascual, DW
DNA免疫虽然很有吸引力，但在诱导粘膜免疫方面效果不佳，从而限制了其对大多数感染性物质的保护价值。为了克服这一缺点，我们设计了一种黏膜转基因疫苗的方法，通过使用M细胞配体将DNA疫苗定向到粘膜诱导组织和呼吸道上皮细胞。这种配体，呼肠孤病毒蛋白Sigma1，当连接到多聚赖氨酸(PL)时，可以结合来自鼻相关淋巴组织的M细胞的顶面。用蛋白Sigma1-PL-DNA复合体进行鼻腔免疫，可产生抗原特异性的血清IGC，延长粘膜IgA，并增强细胞免疫，表现为肺细胞毒性T淋巴细胞反应增加。因此，靶向转基因疫苗是实现粘膜DNA疫苗的一种方法。
DNA immunization, although attractive, is poor for inducing mucosal immunity, thus limiting its protective value against most infectious agents. To surmount this shortcoming, we devised a method for mucosal transgene vaccination by using an M cell ligand to direct the DNA vaccine to mucosal inductive tissues and the respiratory epithelium. This ligand, reovirus protein sigma1, when conjugated to polylysine (PL), can bind the apical surface of M cells from nasal-associated lymphoid tissues. Intranasal immunizations with protein sigma1-PL-DNA complexes produced antigen-specific serum IgC and prolonged mucosal IgA, as well as enhanced cell-mediated immunity, made evident by elevated pulmonary cytotoxic T lymphocyte responses. Therefore, targeted transgene vaccination represents an approach for enabling DNA vaccination of the mucosa.