Mason Peter W, Shustov Alexandr V, Frolov Ilya
Department of Microbiology and Immunology, University of Texas Medical Branch, 301 University Boulevard, Galveston, TX 77555-1019, USA.
Virology. 2006 Aug 1;351(2):432-43. doi: 10.1016/j.virol.2006.04.003. Epub 2006 May 18.
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.
为开发针对黄病毒感染的新型候选疫苗，我们构建了两种复制缺陷型黄病毒，即黄热病毒（YFV）和西尼罗河病毒（WNV）。这些缺陷型假感染病毒（PIV）在其基因组中缺乏衣壳（C）基因的功能性拷贝，在体内和体外感染细胞后均无法引起扩散感染。然而，它们会以分泌性亚病毒颗粒（SVP）的形式产生细胞外E蛋白，已知该蛋白是一种有效的免疫原。PIV可在转互补细胞系中高效繁殖，这些细胞系可产生高水平的C蛋白或所有三种病毒结构蛋白。源自YFV和WNV的PIV表现出极高的安全性，免疫接种可产生高水平的中和抗体和保护性免疫反应。这种缺陷型黄病毒可在低生物安全条件下大规模生产，应可用于诊断或疫苗应用。
