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

Alexander Bukreyev, Andrea Marzi, Friederike Feldmann, Liqun Zhang, Lijuan Yang, Jerrold M. Ward, David W. Dorward, Raymond J. Pickles, Brian R. Murphy, Heinz Feldmann, Peter L. Collins

Research output: Contribution to journalArticle

51 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)348-361
Number of pages14
JournalVirology
Volume383
Issue number2
DOIs
StatePublished - Jan 20 2009
Externally publishedYes

Keywords

  • Antibody
  • Ebola virus
  • Vaccine
  • Vector

ASJC Scopus subject areas

  • Virology

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  • Cite this

    Bukreyev, A., Marzi, A., Feldmann, F., Zhang, L., Yang, L., Ward, J. M., Dorward, D. W., Pickles, R. J., Murphy, B. R., Feldmann, H., & Collins, P. L. (2009). Chimeric human parainfluenza virus bearing the Ebola virus glycoprotein as the sole surface protein is immunogenic and highly protective against Ebola virus challenge. Virology, 383(2), 348-361. https://doi.org/10.1016/j.virol.2008.09.030