Bluetongue virus without NS3/NS3a expression is not virulent and protects against virulent bluetongue virus challenge
Bluetongue virus without NS3/NS3a expression is not virulent and protects against virulent bluetongue virus challenge
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DOI：
10.1099/vir.0.065615-0
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发表时间：
2014-09-01
影响因子：
3.8
通讯作者：
van Rijn, Piet A.
中科院分区：
文献类型：
--
作者：
Feenstra, Femke;van Gennip, Rene G. P.;van Rijn, Piet A.
蓝舌病是一种由蓝舌病病毒（BTV）引起的反刍动物疾病，由库蠓叮咬蠓传播。蓝舌病的爆发在世界几个地区造成了巨大的经济损失和绵羊死亡。控制BTV最有效的措施是接种疫苗。然而，商业上可获得的疫苗和最近开发的候选疫苗都有几个缺点。因此，我们基于BTV-1、无毒力BTV-6或毒性BTV-8的实验室适应株的骨架，生成并测试了下一代蓝舌病疫苗。所有候选疫苗均用BTV-8的VP 2进行血清分型，并且由于NS 3/NS 3a ORF中的诱导缺失而不表达NS 3/NS 3a非结构蛋白。用这些候选疫苗之一对绵羊接种一次，并在接种后3周用强毒BTV-8攻毒。NS 3/NS 3a敲除突变导致所有三种BTV主链完全无毒，包括毒性BTV-8，表明安全性与NS 3/NS 3a敲除表型相关。使用灵敏的PCR诊断法未检出疫苗病毒的病毒血症。显然，疫苗病毒只在局部复制，这将最大限度地减少昆虫媒介的传播。特别是，基于BTV-6骨架的疫苗可预防疾病并预防攻击病毒的病毒血症，显示了该候选疫苗的功效。NS 3/NS 3a表达的缺乏潜在地使得能够区分感染的动物和接种的动物，这对于监测接种的牲畜中的病毒传播是重要的。本文介绍的蓝舌病灭活传染性单动物疫苗是非常有前途的，将是未来研究的主题。
Bluetongue is a disease in ruminants caused by the bluetongue virus (BTV), and is spread by Culicoides biting midges. Bluetongue outbreaks cause huge economic losses and death in sheep in several parts of the world. The most effective measure to control BTV is vaccination. However, both commercially available vaccines and recently developed vaccine candidates have several shortcomings. Therefore, we generated and tested next-generation vaccines for bluetongue based on the backbone of a laboratory-adapted strain of BTV-1, avirulent BTV-6 or virulent BTV-8. All vaccine candidates were serotyped with VP2 of BTV-8 and did not express NS3/NS3a nonstructural proteins, due to induced deletions in the NS3/NS3a ORF. Sheep were vaccinated once with one of these vaccine candidates and were challenged with virulent BTV-8 3 weeks after vaccination. The NS3/NS3a knockout mutation caused complete avirulence for all three BTV backbones, including for virulent BTV-8, indicating that safety is associated with the NS3/NS3a knockout phenotype. Viraemia of vaccine virus was not detected using sensitive PCR diagnostics. Apparently, the vaccine viruses replicated only locally, which will minimize spread by the insect vector. In particular, the vaccine based on the BTV-6 backbone protected against disease and prevented viraemia of challenge virus, showing the efficacy of this vaccine candidate. The lack of NS3/NS3a expression potentially enables the differentiation of infected from vaccinated animals, which is important for monitoring virus spread in vaccinated livestock. The disabled infectious single-animal vaccine for bluetongue presented here is very promising and will be the subject of future studies.