Recombinant adenovirus vectors activate the alternative complement pathway, leading to the binding of human complement protein C3 independent of anti-Ad antibodies
Recombinant adenovirus vectors activate the alternative complement pathway, leading to the binding of human complement protein C3 independent of anti-Ad antibodies
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DOI：
10.1016/j.ymthe.2004.08.015
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发表时间：
2004-12-01
影响因子：
12.4
通讯作者：
Amalfitano, A
中科院分区：
文献类型：
--
作者：
Jiang, H;Wang, Z;Amalfitano, A
重组腺病毒是人类临床试验中最常用的基因转移载体之一，但同样清楚的是，这种病毒的全身给药将通过宿主先天性和适应性抗病毒免疫反应来满足。先天免疫的一个要素是补体系统，这是一组蛋白质，经过进化，可以快速识别外来微生物和病毒，并在它们进入脆弱的宿主细胞之前将其从循环系统中清除。补体过度激活可通过释放强效细胞因子和过敏毒素和/或通过直接细胞毒性来引发或传播许多有害的炎症反应。这些反应可以迅速进展，并且是严重并发症的重要因素，包括全身炎症反应综合征和成人呼吸窘迫综合征。
Recombinant adenoviruses are one of the most common gene transfer vectors utilized in human clinical trials, but it is also clear that systemic administration of this virus will be met by host innate and adaptive antiviral immune responses. One element of innate immunity is the complement system, a group of proteins that has evolved to rapidly recognize foreign microbes and viruses and to clear them from the circulatory system prior to their gaining entry to vulnerable host cells. Excessive complement activation can initiate or propagate a number of deleterious inflammatory responses, by release of potent cytokines and anaphylatoxins and/or by direct cellular toxicity. These reactions can progress rapidly and are factors important in serious complications, including the systemic inflammatory response syndrome and the adult respiratory distress syndrome.