Reap Elizabeth A, Morris John, Dryga Sergey A, Maughan Maureen, Talarico Todd, Esch Robert E, Negri Sarah, Burnett Bruce, Graham Andrew, Olmsted Robert A, Chulay Jeffrey D
AlphaVax Inc., Research Triangle Park, NC 27709, USA.
Vaccine. 2007 Oct 16;25(42):7441-9. doi: 10.1016/j.vaccine.2007.08.016. Epub 2007 Aug 30.
We used a replication-incompetent, single-cycle, alphavirus replicon vector system to produce virus-like replicon particles (VRP) expressing the extracellular domain of human cytomegalovirus (CMV) glycoprotein B or a pp65/IE1 fusion protein. Efficient production methods were scaled to produce pilot lots and clinical lots of each alphavirus replicon vaccine component. The vaccine induced high-titered antibody responses in mice and rabbits, as measured by ELISA and CMV neutralization assays, and robust T-cell responses in mice, as measured by IFN-gamma ELISPOT assay. A toxicity study in rabbits showed no adverse effects in any toxicology parameter. These studies support clinical testing of this novel CMV alphavirus replicon vaccine in humans.
我们使用了一种无复制能力的单周期甲病毒复制子载体系统来生产表达人巨细胞病毒（CMV）糖蛋白B胞外结构域或pp65/IE1融合蛋白的病毒样复制子颗粒（VRP）。高效的生产方法经扩大规模后用于生产每种甲病毒复制子疫苗成分的中试批次和临床批次。通过ELISA和CMV中和试验检测，该疫苗在小鼠和兔子中诱导了高滴度抗体反应，通过IFN-γ ELISPOT试验检测，在小鼠中诱导了强烈的T细胞反应。一项对兔子的毒性研究表明，任何毒理学参数均未出现不良反应。这些研究支持对这种新型CMV甲病毒复制子疫苗进行人体临床试验。
