title: Protection against respiratory syncytial virus by a recombinant Newcastle disease virus vector.
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-alpha/beta) 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-alpha/beta receptor.
authors.affiliation: Columbus Children's Research Institute, 700 Children's Drive, WA-4104, Columbus, OH 43205, USA.
authors.forename: Luis
authors.initials: L
authors.lastname: Martinez-Sobrido
authors.forename: Negin
authors.initials: N
authors.lastname: Gitiban
authors.forename: Ana
authors.initials: A
authors.lastname: Fernandez-Sesma
authors.forename: Jerome
authors.initials: J
authors.lastname: Cros
authors.forename: Sara E
authors.initials: SE
authors.lastname: Mertz
authors.forename: Nancy A
authors.initials: NA
authors.lastname: Jewell
authors.forename: Sue
authors.initials: S
authors.lastname: Hammond
authors.forename: Emilio
authors.initials: E
authors.lastname: Flano
authors.forename: Russell K
authors.initials: RK
authors.lastname: Durbin
authors.forename: Adolfo
authors.initials: A
authors.lastname: García-Sastre
authors.forename: Joan E
authors.initials: JE
authors.lastname: Durbin
mesh_terms: D000818:Animals; D001483:Base Sequence; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002454:Cell Differentiation; D002460:Cell Line; D002522:Chlorocebus aethiops; D004279:DNA, Viral / Q000235:genetics; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology; D005822:Genetic Vectors; D006801:Humans; D016898:Interferon-alpha / Q000096:biosynthesis; D016899:Interferon-beta / Q000096:biosynthesis; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D009522:Newcastle disease virus / Q000235:genetics*; D053633:Receptor, Interferon alpha-beta; D017471:Receptors, Interferon / Q000172:deficiency / Q000235:genetics; D018357:Respiratory Syncytial Virus Infections / Q000276:immunology / Q000473:pathology / Q000517:prevention & control; D022261:Respiratory Syncytial Virus Vaccines / Q000235:genetics / Q000276:immunology / Q000494:pharmacology; D012136:Respiratory Syncytial Viruses / Q000235:genetics / Q000276:immunology* / Q000472:pathogenicity*; D014614:Vaccines, Synthetic / Q000235:genetics / Q000276:immunology / Q000494:pharmacology; D014709:Vero Cells; D014760:Viral Fusion Proteins / Q000235:genetics / Q000276:immunology
chemical_list: D004279:DNA, Viral; D016898:Interferon-alpha; D017471:Receptors, Interferon; D022261:Respiratory Syncytial Virus Vaccines; D014614:Vaccines, Synthetic; D014760:Viral Fusion Proteins; D053633:Receptor, Interferon alpha-beta; D016899:Interferon-beta