Characterization of a family of chimpanzee adenoviruses and development of molecular clones for gene transfer vectors
Characterization of a family of chimpanzee adenoviruses and development of molecular clones for gene transfer vectors
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DOI：
10.1089/10430340460745838
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发表时间：
2004-05-01
影响因子：
4.2
通讯作者：
Wilson, JM
中科院分区：
文献类型：
--
作者：
Roy, S;Gao, GP;Wilson, JM
由于对常用的腺病毒载体预先存在的高度免疫，以及在多种治疗应用中需要重新施用载体，因此有必要开发一组免疫上不同的腺病毒载体，这些载体在人群中很少有中和抗体。我们已经完成了三种黑猩猩衍生的腺病毒，Pan 5、Pan 6和Pan 7的测序，并从每种腺病毒中分子克隆了e1缺失的载体基因组作为细菌质粒。所有的e1缺失载体在HEK 293细胞中培养到高滴度。在人类受试者的血清样本中未检测到黑猩猩腺病毒载体的中和抗体。兔抗血清体外交叉中和和小鼠体内再给药实验表明，针对Pan 5、Pan 7和Pan 9的抗体相互交叉中和，但不中和Pan 6。这些结果表明，黑猩猩腺病毒载体可能可用作人类群体的疫苗或基因治疗载体，并应允许需要多次载体施用的应用。
The high prevalence of preexisting immunity to the commonly used adenoviral vectors, as well as the requirement for readministration of vector for multiple therapeutic applications, necessitates the development of a panel of immunologically distinct adenoviral vectors against which neutralizing antibodies are rare in human populations. We have completely sequenced three chimpanzee-derived adenoviruses, Pan 5, Pan 6, and Pan 7, and have molecularly cloned E1-deleted vector genomes from each as bacterial plasmids. All the E1-deleted vectors were grown to high titer in HEK 293 cells. Neutralizing antibodies to the chimpanzee adenoviral vectors were not detected in serum samples from human subjects. In vitro cross-neutralization using rabbit antisera and in vivo readministration experiments in mice demonstrated that antibodies against Pan 5, Pan 7, or Pan 9 cross-neutralize one another but do not neutralize Pan 6. These results indicate that chimpanzee adenoviral vectors may be useful as vaccines or gene therapy vectors in human populations and should allow applications that require multiple vector administrations.