Effective post-exposure treatment of Ebola infection
Effective post-exposure treatment of Ebola infection
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DOI：
10.1371/journal.ppat.0030002
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发表时间：
2007-01-01
期刊：
影响因子：
6.7
通讯作者：
Geisbert, Thomas W.
中科院分区：
文献类型：
--
作者：
Feldmann, Heinz;Jones, Steven M.;Geisbert, Thomas W.
埃博拉病毒是一种高度致命的人类病原体，近年来由于在中非重新出现并有可能用作生物武器而受到相当大的关注。目前还没有批准用于人类的疫苗或治疗方法。然而，在过去，在开发在动物模型中具有保护性的预防性疫苗方面取得了重要进展。在这方面，我们表明，单次注射表达埃博拉病毒糖蛋白的减毒重组水泡性口炎病毒载体完全保护啮齿动物和非人灵长类动物免受致命的埃博拉病毒攻击。相比之下，在制定针对埃博拉病毒感染的治疗干预措施方面的进展要慢得多，显然迫切需要制定有效的实验后战略，以应对未来的爆发和生物恐怖主义行为，以及治疗实验室暴露。在这里，我们测试了基于水泡性口炎病毒的埃博拉疫苗载体在三种相关动物模型中暴露后治疗的功效。在豚鼠和小鼠模型中，给药后至致死性攻毒后24 h，可分别保护50%和100%的动物。更重要的是，如果在感染后20至30分钟进行治疗，八只恒河猴中有四只受到保护。目前，这种方法为埃博拉感染提供了最有效的暴露后治疗策略，特别适用于意外暴露的个人，以及在自然发生的爆发或故意释放期间控制二次传播。
Ebola viruses are highly lethal human pathogens that have received considerable attention in recent years due to an increasing re-emergence in Central Africa and a potential for use as a biological weapon. There is no vaccine or treatment licensed for human use. In the past, however, important advances have been made in developing preventive vaccines that are protective in animal models. In this regard, we showed that a single injection of a live-attenuated recombinant vesicular stomatitis virus vector expressing the Ebola virus glycoprotein completely protected rodents and nonhuman primates from lethal Ebola challenge. In contrast, progress in developing therapeutic interventions against Ebola virus infections has been much slower and there is clearly an urgent need to develop effective postexposure strategies to respond to future outbreaks and acts of bioterrorism, as well as to treat laboratory exposures. Here we tested the efficacy of the vesicular stomatitis virus-based Ebola vaccine vector in post-exposure treatment in three relevant animal models. In the guinea pig and mouse models it was possible to protect 50% and 100% of the animals, respectively, following treatment as late as 24 h after lethal challenge. More important, four out of eight rhesus macaques were protected if treated 20 to 30 min following an otherwise uniformly lethal infection. Currently, this approach provides the most effective post-exposure treatment strategy for Ebola infections and is particularly suited for use in accidentally exposed individuals and in the control of secondary transmission during naturally occurring outbreaks or deliberate release.