Single-dose attenuated Vesiculovax vaccines protect primates against Ebola Makona virus.
Single-dose attenuated Vesiculovax vaccines protect primates against Ebola Makona virus.
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DOI：
10.1038/nature14428
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发表时间：
2015-04-30
期刊：
影响因子：
64.8
通讯作者：
Geisbert TW
中科院分区：
文献类型：
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作者：
Mire CE;Matassov D;Geisbert JB;Latham TE;Agans KN;Xu R;Ota-Setlik A;Egan MA;Fenton KA;Clarke DK;Eldridge JH;Geisbert TW
丝状病毒科包括埃博拉病毒（EBOV）、马尔堡病毒和库瓦病毒三个属。埃博拉病毒属的一些成员，包括扎伊尔埃博拉病毒（ZEBOV），可引起人类致命的出血热。2014年，西非爆发了前所未有的ZEBOV疫情，目前疫情仍在持续，造成近1万人死亡，并引起全球对疾病失控的关注。为了应对这一挑战，需要一种速效疫苗。许多疫苗方法已经显示出能够保护非人灵长类动物（NHPs）免受ZEBOV感染的希望。为应对目前的ZEBOV疫情，其中一些疫苗已被快速追踪供人使用。然而，尚不清楚这些疫苗中是否有任何一种能够预防新爆发的马科纳ZEBOV毒株。其中一种方法是基于表达ZEBOV糖蛋白（rVSV/ZEBOV）的第一代重组水疱性口炎病毒（rVSV）疫苗。为了解决与该载体相关的安全性问题，我们开发了两种候选的进一步减毒的rVSV/ZEBOV疫苗。与第一代疫苗相比，这两种减毒疫苗产生的疫苗相关病毒血症降低了约10倍，并且都提供了完整的单剂量保护，使猕猴免受马科纳ZEBOV暴发毒株的致命攻击。
The family Filoviridae contains three genera, Ebolavirus (EBOV), Marburg virus, and Cuevavirus. Some members of the EBOV genus, including Zaire ebolavirus (ZEBOV), can cause lethal hemorrhagic fever in humans. During 2014 an unprecedented ZEBOV outbreak occurred in West Africa and is still ongoing, resulting in nearly 10,000 deaths, and causing global concern of uncontrolled disease. To meet this challenge a rapid acting vaccine is needed. Many vaccine approaches have shown promise in being able to protect nonhuman primate (NHPs) against ZEBOV. In response to the current ZEBOV outbreak several of these vaccines have been fast tracked for human use. However, it is not known whether any of these vaccines can provide protection against the new outbreak Makona strain of ZEBOV. One of these approaches is a first generation recombinant vesicular stomatitis virus (rVSV)-based vaccine expressing the ZEBOV glycoprotein (GP) (rVSV/ZEBOV). To address safety concerns associated with this vector, we developed two candidate, further attenuated rVSV/ZEBOV vaccines. Both attenuated vaccines produced an approximately ten-fold lower vaccine-associated viremia compared to the first generation vaccine and both provided complete, single dose protection of macaques from lethal challenge with the Makona outbreak strain of ZEBOV.