M cell DNA vaccination for CTL immunity to HIV
M cell DNA vaccination for CTL immunity to HIV
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DOI：
10.4049/jimmunol.171.9.4717
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发表时间：
2003-11-01
影响因子：
4.4
通讯作者：
Pascual, DW
中科院分区：
文献类型：
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作者：
Wang, XH;Hone, DM;Pascual, DW
为了促进侵入，呼肠孤病毒已经进化为附着于M细胞，M细胞是位于覆盖粘膜诱导组织的滤泡相关上皮内的特化上皮。因此，我们质疑调整呼肠孤病毒蛋白sigma 1将DNA疫苗运送到粘膜以免疫HIV。通过鼻内途径在小鼠中检测了编码HIV（Ba-L）gp 160、胞质gp 140和分泌型gp 140的三种表达质粒，作为蛋白σ 1-聚-L-赖氨酸-DNA复合物（配制疫苗）。细胞介导的免疫评价表明，配制的gp 160 DNA疫苗更有效地刺激肺，下呼吸道淋巴结（LN），颈部LN，颌下腺LN和脾脏的包膜（Env）特异性CTL反应。CTL应答需要三剂疫苗，鼻内裸DNA免疫无效。最大的CTL活性在第8周和第10周之间观察到gp 160疫苗接种的小鼠，活性在第16周仍然可检测到。这些Env特异性CTL应答在外周组织中是穿孔素依赖的，但在肺中主要是Fas依赖的。这些Env特异性CTL还产生IFN-γ。用配制的gp 160 DNA疫苗接种的小鼠显示出对牛痘病毒-em在卵巢中复制的有效抗病毒免疫。因此，与活载体相比，蛋白质σ 1介导的DNA递送代表了用于诱导针对HIV-1的细胞免疫的替代粘膜制剂。
To facilitate invasion, reovirus has evolved to attach to M cells, a specialized epithelium residing within the follicle-associated epithelium that covers mucosal inductive tissues. Thus, we questioned adapting reovirus protein sigma1 to ferry DNA vaccines to the mucosa to immunize against HIV. Three expression plasmids encoding HIV(Ba-L) gp160, cytoplasmic gp140, and secreted gp140 were tested in mice as protein sigma1-poly-L-lysine-DNA complexes (formulated vaccine) via the intranasal route. Evaluation of cell-mediated immunity showed that the formulated gp160 DNA vaccine was more effective for stimulating envelope (Env)-specific CTL responses in lungs, lower respiratory lymph nodes (LN), cervical LN, submaxillary gland LN, and spleens. Three doses of vaccine were required for CTL responses, and intranasal naked DNA immunizations were ineffective. The greatest CTL activity was observed between weeks 8 and 10 for gp160-vaccinated mice, and activity remained detectable by week 16. These Env-specific CTL responses were perforin dependent in peripheral tissues, but mostly Fas dependent in the lungs. These Env-specific CTLs also produced IFN-gamma. Mice vaccinated with the formulated gp160 DNA vaccine showed potent antiviral immunity against vaccinia virus-em, replication in ovaries. Thus, compared with live vectors, protein sigma1-mediated DNA delivery represents an alternative mucosal formulation for inducing cellular immunity against HIV-1.