Protection against respiratory syncytial virus by a recombinant Newcastle disease virus vector

Luis Martinez-Sobrido, Negin Gitiban, Ana Fernandez-Sesma, Jerome Cros, Sara E. Mertz, Nancy A. Jewell, Sue Hammond, Emilio Flano, Russell K. Durbin, Adolfo García-Sastre, Joan E. Durbin

Research output: Contribution to journalArticlepeer-review

107 Scopus citations

Abstract

Respiratory syncytial virus (RSV) is a major cause of severe lower respiratory tract disease in infants and the elderly, but no safe and effective RSV vaccine is yet available. For reasons that are not well understood, RSV is only weakly immunogenic, and reinfection occurs throughout life. This has complicated the search for an effective live attenuated viral vaccine, and past trials with inactivated virus preparations have led to enhanced immunopathology following natural infection. We have tested the hypothesis that weak stimulation of innate immunity by RSV correlates with ineffective adaptive responses by asking whether expression of the fusion glycoprotein of RSV by Newcastle disease virus (NDV) would stimulate a more robust immune response to RSV than primary RSV infection. NDV is a potent inducer of both alpha/beta interferon (IFN-α/β) production and dendritic cell maturation, while RSV is not. When a recombinant NDV expressing the RSV fusion glycoprotein was administered to BALB/c mice, they were protected from RSV challenge, and this protection correlated with a robust anti-F CD8+ T-cell response. The effectiveness of this vaccine construct reflects the differential abilities of NDV and RSV to promote dendritic cell maturation and is retained even in the absence of a functional IFN-α/β receptor.

Original languageEnglish (US)
Pages (from-to)1130-1139
Number of pages10
JournalJournal of virology
Volume80
Issue number3
DOIs
StatePublished - Feb 2006
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

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