Engineered lentivector targeting of dendritic cells for in vivo immunization
Engineered lentivector targeting of dendritic cells for in vivo immunization
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DOI：
10.1038/nbt1390
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发表时间：
2008-03-01
影响因子：
46.9
通讯作者：
Wang, Pin
中科院分区：
文献类型：
--
作者：
Yang, Lili;Yang, Haiguang;Wang, Pin
我们报告了一种通过体内靶向与树突状细胞表面蛋白DC-SIGN特异性结合的慢病毒载体诱导树突状细胞中抗原产生的方法。为了靶向树突状细胞，我们用来自辛德毕斯病毒的病毒糖蛋白包封慢病毒载体，该病毒糖蛋白被工程化为DC-SIGN特异性的。在体外，该慢病毒载体特异性转导树突状细胞并诱导树突状细胞成熟。在将编码OVA转基因的靶向慢病毒载体注射到幼稚小鼠中后2周，观察到高频率（高达12%）的卵清蛋白（OVA）特异性CD 8（+）T细胞和显著的抗体应答。这种方法还防止了表达OVA的E.G7肿瘤的生长，并诱导了已建立的肿瘤的消退。因此，靶向树突状细胞的慢病毒载体提供了一种产生有效免疫的简单方法，并且可以提供用蛋白质抗原免疫的替代途径。
We report a method of inducing antigen production in dendritic cells by in vivo targeting with lentiviral vectors that specifically bind to the dendritic cell-surface protein DC-SIGN. To target dendritic cells, we enveloped the lentivector with a viral glycoprotein from Sindbis virus engineered to be DC-SIGN-specific. In vitro, this lentivector specifically transduced dendritic cells and induced dendritic cell maturation. A high frequency ( up to 12%) of ovalbumin ( OVA)- specific CD8(+) T cells and a significant antibody response were observed 2 weeks after injection of a targeted lentiviral vector encoding an OVA transgene into naive mice. This approach also protected against the growth of OVA-expressing E.G7 tumors and induced regression of established tumors. Thus, lentiviral vectors targeting dendritic cells provide a simple method of producing effective immunity and may provide an alternative route for immunization with protein antigens.