[转移贴]DNA疫苗新策略

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原帖由论坛会员Rojjer发表于 2008-3-17 21:25 |

One strategy being pursued to develop new vaccines against infectious diseases is DNA vaccination. The idea is that following administration of a DNA vaccine, the body converts the information in the DNA vaccine into a protein that activates an immune response. However, current DNA vaccines induce relatively weak immune responses even if administered multiple times. New data, generated in mice, by Ralph Steinman and colleagues, at the Rockefeller University, New York, has now identified a way to make DNA vaccines more potent.

In the study, mice were administered a DNA vaccine that included the information to make a single protein comprised of the HIV protein gp41 fused to a single-chain Fv antibody specific for DEC205. DEC205 is expressed by immune cells known as DCs, which show proteins from infectious organisms to immune cells known as T cells that then attack the infectious organism. The authors found that the single-chain Fv antibody specific for DEC205 targeted the protein made from the information in the DNA vaccine to DCs, such that it was expressed exclusively in DCs. Furthermore, this DNA vaccine induced a much stronger T cell response than DNA vaccines including information to make the HIV protein gp41 fused to an irrelevant single-chain Fv antibody, and it protected mice more efficiently from a virus engineered to express the HIV protein gp41. These data led to the suggestion that DNA vaccines might be more potent if the information they contain generates a protein that is targeted to DCs, for example by fusion to a single-chain Fv antibody specific for a DC surface molecule.



相关知识：
1，单链抗体（single chain antibody，SCA或single chain Fv，ScFv）是新型重组蛋白，由抗体重链可变区（VH）和轻链可变区（VL）通过一段15～25氨基酸残基构成的弹性短肽（Linker）相连而成。单链抗体具有自身的一系列特点：（1）只含有抗体的V区，却能保持较完整的抗原结合位点；（2）缺乏Fc段，不与非靶细胞结合，有利于作为药物的导向载体，运用于临床；（3）免疫原性低；（4）分子量小，容易穿透血管壁、组织及实体瘤；（5）体内血循环半衰期短，易从血循环中排除；（6）在其基因的3’端连接适当的目的分子，如：酶、毒素、药物等可构建双功能抗体；（7）能直接与肿瘤细胞、病毒表面上的抗原结合；（8）由于分子量小，在大肠杆菌中的表达优于完整抗体；（9）因只能与抗原结合，不能激活补体介导细胞免疫；（10）由于是单价抗体，仅有一个抗原结合位点，其亲和力和稳定性较单抗低。

2，DEC205为树突细胞特异性表达分子（具有表达摄取和转运抗原的特殊膜受体）目前发现發現 DEC205 分子可增強 DC 抗原呈現能力， Ralph Steinman 更進一步發現 DEC205 是 DC endocytosis 的重要分子。

“The efficacy of DNA vaccination is enhanced in mice by targeting the encoded protein to dendritic cells”

通过单链抗体把表达的蛋白直接定位于APC上，增强了抗原递呈，解决了向来DNA疫苗抗原递呈效果弱的弊端，个人认为值得进一步研究！
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