@article{14d29c09a08944998feeface43a00a79,
title = "Chimeric human parainfluenza virus bearing the Ebola virus glycoprotein as the sole surface protein is immunogenic and highly protective against Ebola virus challenge",
abstract = "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.",
keywords = "Antibody, Ebola virus, Vaccine, Vector",
author = "Alexander Bukreyev and Andrea Marzi and Friederike Feldmann and Liqun Zhang and Lijuan Yang and Ward, {Jerrold M.} and Dorward, {David W.} and Pickles, {Raymond J.} and Murphy, {Brian R.} and Heinz Feldmann and Collins, {Peter L.}",
note = "Funding Information: We are grateful to Dr. Anthony Sanchez (Centers for Disease Control and Prevention, Atlanta, Georgia) for providing gamma-irradiated purified EBOV antigen for ELISA, rabbit immune serum against EBOV and guinea pig serum specific for EBOV GP. We thank Ernest Williams and Fatemeh Davoodi for performing HAI assays, Alison Bright and her staff for animal care work and collection of serum samples, and Lawrence J. Faucette and Elizabeth M. Williams for histotechnology assistance. We also thank Jason Gren, National Microbiology Laboratory, Public Health Agency of Canada, for assistance with animal care in high biocontainment. We are grateful to the Directors and teams of the UNC Cystic Fibrosis Center Tissue Culture Core, the Morphology and Morphometry Core and the Michael Hooker Microscopy Facility for supplying reagents and technical expertise and to Susan Burkett for technical assistance. This project was funded as a part of the NIAID Intramural Program, Public Health Agency of Canada, and the National Institutes of Health (NIH) grant NIH R01 HL77844-1.",
year = "2009",
month = jan,
day = "20",
doi = "10.1016/j.virol.2008.09.030",
language = "English (US)",
volume = "383",
pages = "348--361",
journal = "Virology",
issn = "0042-6822",
publisher = "Academic Press Inc.",
number = "2",
}