title: Consecutive CT in vivo lung imaging as quantitative parameter of influenza vaccine efficacy in the ferret model.
abstract: Preclinical vaccine efficacy studies are generally limited to certain read out parameters such as assessment of virus titers in swabs and organs, clinical signs, serum antibody titers, and pathological changes. These parameters are not always routinely applied and not always scheduled in a logical standardized way. We used computed tomography (CT) imaging as additional and novel read out parameter in a vaccine efficacy study by quantifying alterations in aerated lung volumes in ferrets challenged with the 2009 pandemic A/H1N1 influenza virus. Vaccination protected from marked variations in aerated lung volumes compared to naive controls. The vaccinated group showed a daily gradual mean reduction with a maximum of 7.8%, whereas the controls showed a maximum of 14.3% reduction. The pulmonary opacities evident on CT images were most pronounced in the placebo-treated controls, and corresponded to significantly increased relative lung weights at necropsy. This study shows that consecutive in vivo CT imaging allows for a day to day read out of vaccine efficacy by quantification of altered aerated lung volumes.
authors.affiliation: ViroClinics Biosciences B.V., 3000 DR Rotterdam, The Netherlands.
authors.forename: Edwin J B
authors.initials: EJ
authors.lastname: Veldhuis Kroeze
authors.forename: Koert J
authors.initials: KJ
authors.lastname: Stittelaar
authors.forename: Vera J
authors.initials: VJ
authors.lastname: Teeuwsen
authors.forename: Marcel L
authors.initials: ML
authors.lastname: Dijkshoorn
authors.forename: Geert
authors.initials: G
authors.lastname: van Amerongen
authors.forename: Leon
authors.initials: L
authors.lastname: de Waal
authors.forename: Thijs
authors.initials: T
authors.lastname: Kuiken
authors.forename: Gabriel P
authors.initials: GP
authors.lastname: Krestin
authors.forename: Jorma
authors.initials: J
authors.lastname: Hinkula
authors.forename: Albert D M E
authors.initials: AD
authors.lastname: Osterhaus
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D055808:Drug Discovery / Q000379:methods; D005260:Female; D005289:Ferrets; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000276:immunology*; D008168:Lung / Q000000981:diagnostic imaging / Q000473:pathology*; D009976:Orthomyxoviridae Infections / Q000473:pathology / Q000517:prevention & control*; D010336:Pathology / Q000379:methods*; D010919:Placebos / Q000008:administration & dosage; D014057:Tomography, X-Ray Computed / Q000379:methods*; D016896:Treatment Outcome
chemical_list: D007252:Influenza Vaccines; D010919:Placebos