Sullivan N J, Sanchez A, Rollin P E, Yang Z Y, Nabel G J
Vaccine Research Center, National Institutes of Health, Bethesda, Maryland 20892, USA.
Nature. 2000 Nov 30;408(6812):605-9. doi: 10.1038/35046108.
Outbreaks of haemorrhagic fever caused by the Ebola virus are associated with high mortality rates that are a distinguishing feature of this human pathogen. The highest lethality is associated with the Zaire subtype, one of four strains identified to date. Its rapid progression allows little opportunity to develop natural immunity, and there is currently no effective anti-viral therapy. Therefore, vaccination offers a promising intervention to prevent infection and limit spread. Here we describe a highly effective vaccine strategy for Ebola virus infection in non-human primates. A combination of DNA immunization and boosting with adenoviral vectors that encode viral proteins generated cellular and humoral immunity in cynomolgus macaques. Challenge with a lethal dose of the highly pathogenic, wild-type, 1976 Mayinga strain of Ebola Zaire virus resulted in uniform infection in controls, who progressed to a moribund state and death in less than one week. In contrast, all vaccinated animals were asymptomatic for more than six months, with no detectable virus after the initial challenge. These findings demonstrate that it is possible to develop a preventive vaccine against Ebola virus infection in primates.
由埃博拉病毒引起的出血热疫情与高死亡率相关,这是这种人类病原体的一个显著特征。最高致死率与扎伊尔亚型有关,它是迄今为止确定的四种毒株之一。其快速发展使得几乎没有机会产生自然免疫力,而且目前没有有效的抗病毒疗法。因此,接种疫苗是预防感染和限制传播的一种有前景的干预措施。在此,我们描述了一种针对非人类灵长类动物埃博拉病毒感染的高效疫苗策略。DNA免疫与编码病毒蛋白的腺病毒载体加强免疫相结合,在食蟹猕猴中产生了细胞免疫和体液免疫。用高致病性、野生型、1976年马英加株埃博拉扎伊尔病毒的致死剂量进行攻毒,对照组均被感染,在不到一周的时间内病情发展至濒死状态并死亡。相比之下,所有接种疫苗的动物在六个多月的时间里均无症状,初次攻毒后未检测到病毒。这些发现表明,有可能开发出一种针对灵长类动物埃博拉病毒感染的预防性疫苗。