A replication-competent vesicular stomatitis virus vaccine expressing the Ebola virus (EBOV) glycoprotein (GP) (rVSV-ZEBOV) was successfully used during the 2013-16 EBOV epidemic. Additionally, chimeric and human monoclonal antibodies (mAb) against the EBOV GP have shown promise in animals and humans when administered therapeutically. Uncertainty exists regarding the efficacy of postexposure antibody treatments in the event of a known exposure of a recent rVSV-ZEBOV vaccinee. Here, we model a worst-case scenario using rhesus monkeys vaccinated or unvaccinated with the rVSV-ZEBOV vaccine. We demonstrate that animals challenged with a uniformly lethal dose of EBOV one day following vaccination, and then treated with the anti-EBOV GP mAb MIL77 starting 3 days postexposure show no evidence of clinical illness and survive challenge. In contrast, animals receiving only vaccination or only mAb-based therapy become ill, with decreased survival compared to animals vaccinated and subsequently treated with MIL77. These results suggest that rVSV-ZEBOV augments immunotherapy.

译文

:在2013-16年度EBOV流行期间,成功使用了具有复制能力的表达埃博拉病毒(EBOV)糖蛋白(GP)(rVSV-ZEBOV)的水疱性口炎病毒疫苗。此外,针对EBOV GP的嵌合和人类单克隆抗体(mAb)在治疗性给药后在动物和人类中显示出了希望。在已知接触最近的rVSV-ZEBOV疫苗的情况下,有关暴露后抗体治疗功效的不确定性。在这里,我们使用接种rVSV-ZEBOV疫苗或未接种rvsv-zebov疫苗的恒河猴对最坏情况进行建模。我们证明,在接种疫苗后的第一天,用均匀致死剂量的EBOV攻击动物,然后在暴露后3天开始用抗EBOV GP mAb MIL77进行治疗,这些动物均未显示出临床疾病的证据,并且可以在攻击中幸存下来。相反,仅接受疫苗接种或仅接受基于mAb的治疗的动物会生病,与接种疫苗并随后接受MIL77治疗的动物相比,存活率降低。这些结果表明,rVSV-ZEBOV增强了免疫治疗。

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