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

被引：55

作者：

Bukreyev, Alexander ^{[1
]}

Marzi, Andrea ^{[2
]}

Feldmann, Friederike ^{[2
]}

Zhang, Liqun ^{[4
]}

Yang, Lijuan ^{[1
]}

Ward, Jerrold M. ^{[1
]}

Dorward, David W. ^{[5
]}

Pickles, Raymond J. ^{[4
]}

Murphy, Brian R. ^{[1
]}

Feldmann, Heinz ^{[2
,3
]}

Collins, Peter L. ^{[1
]}

机构：

[1] NIAID, NIH, Bethesda, MD 20892 USA

[2] Canadian Sci Ctr Human & Anim Hlth, Special Pathogens Program, Natl Microbiol Lab, Winnipeg, MB, Canada

[3] Univ Manitoba, Dept Med Microbiol, Winnipeg, MB R3T 2N2, Canada

[4] Univ N Carolina, Cyst Fibrosis Pulm Res & Treatment Ctr, Chapel Hill, NC USA

[5] NIAID, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA

来源：

VIROLOGY | 2009年 / 383卷 / 02期

基金：

美国国家卫生研究院;

关键词：

Ebola virus; Vaccine; Antibody; Vector; POLARIZED EPITHELIAL-CELLS; VACCINIA VIRUS; RHESUS-MONKEYS; MARBURG VIRUS; HEMAGGLUTININ-NEURAMINIDASE; NEUTRALIZING ANTIBODIES; NUCLEOTIDE-SEQUENCE; ADENOVIRUS VECTORS; ANTI-AD5; IMMUNITY; NONHUMAN-PRIMATES;

D O I：

10.1016/j.virol.2008.09.030

中图分类号：

Q93 [微生物学];

学科分类号：

071005 ; 100705 ;

摘要：

We generated a new live-attenuated vaccine against Ebola virus (EBOV) based on a chimeric virus HPIV3/Delta F-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/Delta F-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/Delta F-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. Published by Elsevier Inc.

引用

页码：348 / 361

页数：14

共 44 条

[21] Safety and immunogenicity of NYVAC-JEV and ALVAC-JEV attenuated recombinant Japanese encephalitis virus - poxvirus vaccines in vaccinia-nonimmune and vaccinia-immune humans [J].