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Development and preclinical evaluation of an alphavirus replicon particle vaccine for cytomegalovirus

机译:用于巨细胞病毒的α病毒复制子颗粒疫苗的开发和临床前评估

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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.
机译:我们使用了无复制能力的单周期α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或pp65 / IE1融合蛋白胞外域的病毒样复制子颗粒(VRP)。缩放有效的生产方法以生产每种α病毒复制子疫苗成分的中试批次和临床批次。通过ELISA和CMV中和测定,该疫苗在小鼠和兔子中诱导出高滴度抗体应答,通过IFN-γELISPOT测定,在小鼠中诱导出强大的T细胞应答。对兔子的毒性研究表明,在任何毒理学参数方面均无不良影响。这些研究支持这种新型CMVα病毒复制子疫苗在人体中的临床测试。

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