Mire Chad E, Matassov Demetrius, Geisbert Joan B, Latham Theresa E, Agans Krystle N, Xu Rong, Ota-Setlik Ayuko, Egan Michael A, Fenton Karla A, Clarke David K, Eldridge John H, Geisbert Thomas W
Galveston National Laboratory, University of Texas Medical Branch, Galveston, TX, USA.
Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX, USA.
Nature. 2015 Apr 30;520(7549):688-691. doi: 10.1038/nature14428. Epub 2015 Apr 8.
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 haemorrhagic fever in humans. During 2014 an unprecedented ZEBOV outbreak occurred in West Africa and is still ongoing, resulting in over 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 primates 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 tenfold lower vaccine-associated viraemia 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.
丝状病毒科包含三个属，即埃博拉病毒属（EBOV）、马尔堡病毒属和库埃瓦病毒属。埃博拉病毒属的一些成员，包括扎伊尔埃博拉病毒（ZEBOV），可导致人类致命性出血热。2014年期间，西非发生了前所未有的扎伊尔埃博拉病毒疫情，目前仍在持续，导致1万多人死亡，引起了全球对疾病失控的担忧。为应对这一挑战，需要一种速效疫苗。许多疫苗研发方法已显示出有望保护非人灵长类动物免受扎伊尔埃博拉病毒感染。针对当前的扎伊尔埃博拉病毒疫情，其中几种疫苗已被快速推进至人体使用阶段。然而，尚不清楚这些疫苗中是否有任何一种能够提供针对扎伊尔埃博拉病毒新爆发的马科纳毒株的保护。其中一种方法是第一代基于重组水疱性口炎病毒（rVSV）的疫苗，该疫苗表达扎伊尔埃博拉病毒糖蛋白（GP）（rVSV/ZEBOV）。为解决与该载体相关的安全问题，我们研发了两种进一步减毒的rVSV/ZEBOV候选疫苗。与第一代疫苗相比，两种减毒疫苗产生的疫苗相关病毒血症均降低了约10倍，并且两种疫苗均能为猕猴提供单剂量的完全保护，使其免受扎伊尔埃博拉病毒马科纳爆发毒株的致命攻击。
