title: Respiratory syncytial virus (RSV)-induced airway hyperresponsiveness in allergically sensitized mice is inhibited by live RSV and exacerbated by formalin-inactivated RSV.
abstract: Respiratory syncytial virus (RSV)-induced disease is associated with recurrent episodes of wheezing in children, and an effective vaccine currently is not available. The use of 2 immunizations (a formalin-inactivated, alum-precipitated RSV vaccine [FI-RSV] given intramuscularly and live RSV given intranasally [LVIN]), with a control immunization, were compared in a well-characterized model of RSV challenge, with or without concomitant allergic sensitization with ovalbumin. FI-RSV caused a significant increase in airway hyperresponsiveness in mice after RSV infection during allergic sensitization, and this was associated with an increase in type 2 cytokine production. In contrast, immunization with LVIN did not change type 2 cytokine production and protected against RSV-induced airway hyperresponsiveness in the setting of allergic sensitization. This study suggests that immune modulation with RSV vaccination can have profound effects on RSV-induced airway disease and that prevention of airway hyperresponsiveness is an important end point in vaccine development.
authors.affiliation: Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-2582, USA. stokes.peebles@mcmail.vanderbilt.edu
authors.forename: R S
authors.initials: RS
authors.lastname: Peebles
authors.forename: J R
authors.initials: JR
authors.lastname: Sheller
authors.forename: R D
authors.initials: RD
authors.lastname: Collins
authors.forename: K
authors.initials: K
authors.lastname: Jarzecka
authors.forename: D B
authors.initials: DB
authors.lastname: Mitchell
authors.forename: B S
authors.initials: BS
authors.lastname: Graham
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D005557:Formaldehyde; D016210:Methacholine Chloride; D051379:Mice; D008807:Mice, Inbred BALB C; D012130:Respiratory Hypersensitivity / Q000139:chemically induced / Q000276:immunology* / Q000821:virology; D018357:Respiratory Syncytial Virus Infections / Q000276:immunology; D012136:Respiratory Syncytial Viruses / Q000187:drug effects / Q000276:immunology*; D015164:Vaccines, Inactivated / Q000008:administration & dosage / Q000276:immunology*; D014765:Viral Vaccines / Q000008:administration & dosage / Q000276:immunology*
chemical_list: D015164:Vaccines, Inactivated; D014765:Viral Vaccines; D016210:Methacholine Chloride; D005557:Formaldehyde