Protection against respiratory syncytial virus by a recombinant Newcastle disease virus vector.
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.
Martinez-Sobrido
Luis
L
Columbus Children's Research Institute, 700 Children's Drive, WA-4104, Columbus, OH 43205, USA.
Gitiban
Negin
N
Fernandez-Sesma
Ana
A
Cros
Jerome
J
Mertz
Sara E
SE
Jewell
Nancy A
NA
Hammond
Sue
S
Flano
Emilio
E
Durbin
Russell K
RK
García-Sastre
Adolfo
A
Durbin
Joan E
JE
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
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