Emerging targets and novel approaches to Ebola virus prophylaxis and treatment.
Emerging targets and novel approaches to Ebola virus prophylaxis and treatment.
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DOI：
10.1007/s40259-013-0046-1
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发表时间：
2013-12
期刊：
影响因子：
--
通讯作者：
Croyle MA
中科院分区：
文献类型：
--
作者：
Choi JH;Croyle MA
埃博拉病毒是一种能引起严重出血热的高致死性病原体，在人类和非人类灵长类动物中病死率很高。尽管目前还没有安全有效的疫苗或其他药物来阻止埃博拉感染，但已经做出了重大努力，以确定几种有望治疗和预防埃博拉出血热的候选药物。其中，基于重组病毒的载体已被确定为有效的候选疫苗，其中一些提供了暴露前和暴露后对病毒的保护。最近，美国(U.S.)批准了研究用新药(IND)申请。美国食品和药物管理局(FDA)和美国食品和药物管理局(FDA)启动了两种小分子疗法的第一阶段临床试验，1)反义磷二酸二乙酯吗啡低聚物(PMOS：AVI-6002，AVI-6003)，以及2)脂纳米粒/小干扰RNA(LNP/siRNA：TKM-Ebola)。这些以媒介为基础的疫苗的潜在替代品需要多次剂量才能达到治疗效果，这就患者依从性和暴发情况而言并不理想。这些担忧促使人们寻求更好的疫苗接种和治疗策略。在这里，我们总结了预防埃博拉出血热的疫苗或暴露后治疗方法的最新进展。还将讨论改进和克服与最有前景的治疗平台相关的障碍的新药物方法的效用。
Ebola is a highly virulent pathogen causing severe hemorrhagic fever with a high case fatality rate in humans and non-human primates (NHPs). Although safe and effective vaccines or other medicinal agents to block Ebola infection are currently unavailable, a significant effort has been put forth to identify several promising candidates for the treatment and prevention of Ebola hemorrhagic fever. Among these, recombinant-virus based vectors have been identified as potent vaccine candidates with some affording both pre- and post-exposure protection from the virus. Recently, Investigational New Drug (IND) applications have been approved by the United States (U.S.) Food and Drug Administration (FDA) and Phase I clinical trials initiated for two small molecule therapeutics, 1) anti-sense phosphorodiamidate morphino oligomers (PMOs: AVI-6002, AVI-6003), and 2) lipid-nanoparticle/small interfering RNA (LNP/siRNA: TKM-Ebola). These potential alternatives to vector-based vaccines require multiple doses to achieve therapeutic efficacy which is not ideal with regard to patient compliance and outbreak scenarios. These concerns have fueled a quest for even better vaccination and treatment strategies. Here, we summarize recent advances in vaccines or post-exposure therapeutics for prevention of Ebola hemorrhagic fever. The utility of novel pharmaceutical approaches to refine and overcome barriers associated with the most promising therapeutic platforms will also be discussed.
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