title: Absence of vaccine-enhanced RSV disease and changes in pulmonary dendritic cells with adenovirus-based RSV vaccine.
abstract: The development of a vaccine against respiratory syncytial virus (RSV) has been hampered by the risk for vaccine-enhanced RSV pulmonary disease induced by immunization with formalin-inactivated RSV (FIRSV). This study focuses on the evaluation of vaccine-enhanced pulmonary disease following immunization with AdF.RGD, an integrin-targeted adenovirus vector that expresses the RSV F protein and includes an RGD (Arg-Gly-Asp) motif. Immunization of BALB/c mice with AdF.RGD, resulted in anti-RSV protective immunity and induced increased RSV-specific IFN-γ T cell responses compared to FIRSV. RSV infection 5 wk after immunization with FIRSV induced pulmonary inflammatory responses in the lung, that was not observed with AdF.RGD. Additionally, In the FIRSV-immunized mice following infection with RSV, pulmonary DC increased and Tregs decreased. This suggests that distinct responses of pulmonary DC and Tregs are a features of vaccine-enhanced RSV disease and that immunization with an RGD-modified Ad vaccine does not trigger vaccine-enhanced disease.
authors.affiliation: Department of Genetic Medicine, Weill Medical College of Cornell University, New York, New York, USA.
authors.forename: Anja
authors.initials: A
authors.lastname: Krause
authors.forename: Yaqin
authors.initials: Y
authors.lastname: Xu
authors.forename: Sara
authors.initials: S
authors.lastname: Ross
authors.forename: Wendy
authors.initials: W
authors.lastname: Wu
authors.forename: Ju
authors.initials: J
authors.lastname: Joh
authors.forename: Stefan
authors.initials: S
authors.lastname: Worgall
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D003713:Dendritic Cells / Q000276:immunology*; D004337:Drug Carriers; D005260:Female; D005822:Genetic Vectors; D007371:Interferon-gamma / Q000378:metabolism; D008168:Lung / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D018357:Respiratory Syncytial Virus Infections / Q000276:immunology / Q000517:prevention & control*; D022261:Respiratory Syncytial Virus Vaccines / Q000008:administration & dosage / Q000009:adverse effects* / Q000235:genetics / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000009:adverse effects / Q000235:genetics / Q000276:immunology; D014760:Viral Fusion Proteins / Q000235:genetics / Q000276:immunology*
chemical_list: D004337:Drug Carriers; C526850:F protein, human respiratory syncytial virus; D022261:Respiratory Syncytial Virus Vaccines; D014614:Vaccines, Synthetic; D014760:Viral Fusion Proteins; D007371:Interferon-gamma