Chimeric human parainfluenza virus bearing the Ebola virus glycoprotein as the sole surface protein is immunogenic and highly protective against Ebola virus challenge.

Chimeric human parainfluenza virus bearing the Ebola virus glycoprotein as the sole surface protein is immunogenic and highly protective against Ebola virus challenge.
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DOI:
10.1016/j.virol.2008.09.030
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发表时间:
2009-01-20
期刊:
影响因子:
3.7
通讯作者:
Collins, Peter L.
Collins, Peter L.
中科院分区:
医学3区
文献类型:
--
作者:
Bukreyev, Alexander;Marzi, Andrea;Feldmann, Friederike;Zhang, Liqun;Yang, Lijuan;Ward, Jerrold M.;Dorward, David W.;Pickles, Raymond J.;Murphy, Brian R.;Feldmann, Heinz;Collins, Peter L.

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本研究基于人副流感病毒3型(HPIV 3)的内部蛋白和EBOV糖蛋白(GP)的嵌合病毒HPIV 3/ΔF-HN/EboGP构建了一种新的抗埃博拉病毒(EBOV)减毒活疫苗。病毒颗粒的电子显微镜分析显示,它们具有类似于EBOV的包膜和表面刺突,以及类似于HPIV 3的颗粒大小和形状。当HPIV 3/ΔF-HN/EboGP通过人纤毛气道上皮体外模型的顶面接种时,病毒从顶面释放;当应用于基底面时,病毒感染基底面细胞,但不通过组织扩散。豚鼠鼻内(IN)接种后,通过免疫组织化学在肺中检测到散在的感染细胞,但不能从肺、血液或其他组织中回收感染性HPIV 3/ΔF-HN/EboGP。尽管减毒,但病毒具有高度免疫原性,并且单次IN剂量完全保护动物免受豚鼠适应性EBOV的高度致死性腹膜内攻击。
We generated a new live-attenuated vaccine against Ebola virus (EBOV) based on a chimeric virus HPIV3/ΔF-HN/EboGP that contains the EBOV glycoprotein (GP) as the sole transmembrane envelope protein combined with the internal proteins of human parainfluenza virus type 3 (HPIV3). Electron microscopy analysis of the virus particles showed that they have an envelope and surface spikes resembling those of EBOV and a particle size and shape resembling those of HPIV3. When HPIV3/ΔF-HN/EboGP was inoculated via apical surface of an in vitro model of human ciliated airway epithelium, the virus was released from the apical surface; when applied to basolateral surface, the virus infected basolateral cells but did not spread through the tissue. Following intranasal (IN) inoculation of guinea pigs, scattered infected cells were detected in the lungs by immunohistochemistry, but infectious HPIV3/ΔF-HN/EboGP could not be recovered from the lungs, blood, or other tissues. Despite the attenuation, the virus was highly immunogenic, and a single IN dose completely protected the animals against a highly lethal intraperitoneal challenge of guinea pig-adapted EBOV.
DOI: 10.1016/0042-6822(85)90395-2
发表时间: 1985-01-01
期刊: VIROLOGY
影响因子: 3.7
作者:
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发表时间: 2007-06-01
影响因子: 5.4
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