Wu Y, Wang X, Csencsits K L, Haddad A, Walters N, Pascual D W
Veterinary Molecular Biology, Montana State University, Bozeman, MT 59717-3610, USA.
Proc Natl Acad Sci U S A. 2001 Jul 31;98(16):9318-23. doi: 10.1073/pnas.161204098. Epub 2001 Jul 17.
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 final sigma1, when conjugated to polylysine (PL), can bind the apical surface of M cells from nasal-associated lymphoid tissues. Intranasal immunizations with protein final sigma1-PL-DNA complexes produced antigen-specific serum IgG 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.
DNA免疫尽管具有吸引力,但在诱导黏膜免疫方面效果不佳,因此限制了其对大多数感染因子的保护价值。为克服这一缺点,我们设计了一种黏膜转基因疫苗接种方法,通过使用M细胞配体将DNA疫苗导向黏膜诱导组织和呼吸道上皮。这种配体,呼肠孤病毒蛋白终末σ1,与聚赖氨酸(PL)偶联后,可结合鼻相关淋巴组织M细胞的顶端表面。用蛋白终末σ1-PL-DNA复合物进行鼻内免疫可产生抗原特异性血清IgG和延长的黏膜IgA,以及增强的细胞介导免疫,这通过肺细胞毒性T淋巴细胞反应升高得以体现。因此,靶向转基因疫苗接种是一种实现黏膜DNA疫苗接种的方法。