Production and characterization of vaccines based on flaviviruses defective in replication
Production and characterization of vaccines based on flaviviruses defective in replication
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DOI：
10.1016/j.virol.2006.04.003
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发表时间：
2006-08-01
期刊：
影响因子：
3.7
通讯作者：
Frolov, Ilya
中科院分区：
文献类型：
--
作者：
Mason, Peter W.;Shustov, Alexandr V.;Frolov, Ilya
为了开发用于黄病毒感染的新疫苗候选物，我们已经工程化了两种黄病毒，黄热病病毒（YFV）和西尼罗河病毒（WNV），它们是复制缺陷的。这些缺陷性假感染性病毒（PIV）在其基因组中缺乏衣壳（C）基因的功能性拷贝，并且在体内和体外感染细胞时不能引起扩散性感染。然而，它们以分泌的亚病毒颗粒（SVP）的形式产生细胞外E蛋白，已知其是有效的免疫原。PIV可以在产生高水平C或所有三种病毒结构蛋白的反式互补细胞系中有效繁殖。来自YFV和WNV的PIV显示出非常高的安全性，并且免疫产生高水平的中和抗体和保护性免疫应答。这种缺陷型黄病毒可以在低生物防护条件下大规模生产，并可用于诊断或疫苗应用。(c)2006年爱思唯尔公司All rights reserved.
To develop new vaccine candidates for flavivirus infections, we have engineered two flaviviruses, yellow fever virus (YFV) and West Nile virus (WNV), that are deficient in replication. These defective pseudoinfectious viruses (PIVs) lack a functional copy of the capsid (C) gene in their genomes and are incapable of causing spreading infection upon infection of cells both in vivo and in vitro. However, they produce extracellular E protein in form of secreted subviral particles (SVPs) that are known to be an effective immunogen. PIVs can be efficiently propagated in trans-complementing cell lines making high levels of C or all three viral structural proteins. PIVs derived from YFV and WNV, demonstrated very high safety and immunization produced high levels of neutralizing antibodies and protective immune response. Such defective flaviviruses can be produced in large scale under low biocontainment conditions and should be useful for diagnostic or vaccine applications. (c) 2006 Elsevier Inc. All rights reserved.