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

Journal Article · Tue Jan 20 04:00:00 EST 2009 · Virology

DOI:https://doi.org/10.1016/j.virol.2008.09.030· OSTI ID:21182799

Bukreyev, Alexander ^[1]; Marzi, Andrea; Feldmann, Friederike ^[2]; Liqun, Zhang ^[3]; Lijuan, Yang; Ward, Jerrold M ^[1]; Dorward, David W ^[4]; Pickles, Raymond J ^[3]; Murphy, Brian R ^[1]; Feldmann, Heinz ^[2]; Collins, Peter L ^[1]

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1. National Institute of Allergy and Infectious Diseases, Building 50, Room 6505, NIAID, National Institutes of Health, 50 South Dr. MSC 8007, Bethesda, MD 20892-8007 (United States)
2. Special Pathogens Program, National Microbiology Laboratory, Canadian Science Centre for Human and Animal Health, Winnipeg (Canada)
3. Cystic Fibrosis/Pulmonary Research and Treatment Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina (United States)
4. Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana (United States)

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.

• OSTI ID: 21182799
• Journal Information: Virology, Journal Name: Virology Journal Issue: 2 Vol. 383; ISSN VIRLAX; ISSN 0042-6822
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
ANTIBODIES
BLOOD
ELECTRON MICROSCOPY
EPITHELIUM
GLYCOPROTEINS
GUINEA PIGS
IN VITRO
LUNGS
PARTICLE SIZE
VACCINES
VIRUSES