[转移帖]日研究发现基因疫苗增强免疫的关键

cao1976

原帖由论坛会员hans发表于 2008-2-8 11:58


日本大阪大学研究人员７日报告说，基因疫苗增强免疫系统的关键是能够激活白细胞的双链脱氧核糖核酸（ＤＮＡ），而与之前认为的碱基序列无关。  

        基因疫苗指将编码某种蛋白质抗原的重组真核表达载体直接注射到动物体内，使外源基因在活体内表达，产生的抗原激活机体免疫系统，从而诱导特异性的体液免疫和细胞免疫应答。  

        大阪大学教授审良静男领导的研究小组在７日出版的英国《自然》杂志上发表论文说，他们利用实验鼠研究发现，双链ＤＮＡ进入细胞后会促使一种激酶发挥作用，进而激活白细胞，后者会攻击病原体。而以往的理论认为，拥有特定碱基序列的单链ＤＮＡ附着于受体，从而增强免疫。  
        本项研究显示，双链ＤＮＡ的免疫作用强于单链ＤＮＡ，这为开发安全、高效的基因疫苗开辟了新途径。

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TANK-binding kinase-1 delineates innate and adaptive immune responses to DNA vaccines

Successful vaccines contain not only protective antigen(s) but also an adjuvant component that triggers innate immune activation and is necessary for their optimal immunogenicity1, 2. In the case of DNA vaccines3, this consists of plasmid DNA; however, the adjuvant element(s) as well as its intra- and inter-cellular innate immune signalling pathway(s) leading to the encoded antigen-specific T- and B-cell responses remain unclear. Here we demonstrate in vivo that TANK-binding kinase 1 (TBK1), a non-canonical IB kinase, mediates the adjuvant effect of DNA vaccines and is essential for its immunogenicity in mice. Plasmid-DNA-activated, TBK1-dependent signalling and the resultant type-I interferon receptor-mediated signalling was required for induction of antigen-specific B and T cells, which occurred even in the absence of innate immune signalling through a well known CpG DNA sensor—Toll-like receptor 9 (TLR9) or Z-DNA binding protein 1 (ZBP1, also known as DAI, which was recently reported as a potential B-form DNA sensor4). Moreover, bone-marrow-transfer experiments revealed that TBK1-mediated signalling in haematopoietic cells was critical for the induction of antigen-specific B and CD4+ T cells, whereas in non-haematopoietic cells TBK1 was required for CD8+ T-cell induction. These data suggest that TBK1 is a key signalling molecule for DNA-vaccine-induced immunogenicity, by differentially controlling DNA-activated innate immune signalling through haematopoietic and non-haematopoietic cells.