title: Mucosal expression of DEC-205 targeted allergen alleviates an asthmatic phenotype in mice.
abstract: Considering the rising incidence of allergic asthma, the symptomatic treatments that are currently applied in most cases are less than ideal. Specific immunotherapy is currently the only treatment that is able to change the course of the disease, but suffers from a long treatment duration. A gene based immunization that elicits the targeting of allergens towards dendritic cells in a steady-state environment might have the potential to amend these difficulties. Here we used a replication deficient adenovirus to induce the mucosal expression of OVA coupled to a single-chain antibody against DEC-205. A single intranasal vaccination was sufficient to mitigate an OVA-dependent asthmatic phenotype in a murine model. Invasive airway measurements demonstrated improved lung function after Ad-Dec-OVA treatment, which was in line with a marked reduction of goblet cell hyperplasia and lung eosinophilia. Furthermore OVA-specific IgE titers and production of type 2 cytokines were significantly reduced. Together, the here presented data demonstrate the feasibility of mucosal expression of DEC-targeted allergens as a treatment of allergic asthma.
authors.affiliation: Department of Molecular and Medical Virology, Ruhr-University, Bochum, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Maaske
authors.affiliation: Centre for Environment and Health, Department of Public Health and Primary Care, KU Leuven, Leuven, Belgium.
authors.forename: F C
authors.initials: FC
authors.lastname: Devos
authors.affiliation: Department of Molecular and Medical Virology, Ruhr-University, Bochum, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Niezold
authors.affiliation: Department of Molecular and Medical Virology, Ruhr-University, Bochum, Germany.
authors.forename: D
authors.initials: D
authors.lastname: Lapuente
authors.affiliation: Institute of Pathology, Ruhr University of Bochum, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Tannapfel
authors.affiliation: Centre for Environment and Health, Department of Public Health and Primary Care, KU Leuven, Leuven, Belgium.
authors.forename: J A
authors.initials: JA
authors.lastname: Vanoirbeek
authors.affiliation: Department of Molecular and Medical Virology, Ruhr-University, Bochum, Germany.
authors.forename: K
authors.initials: K
authors.lastname: Überla
authors.affiliation: Department of Experimental Pneumology, Ruhr University Bochum, Bochum, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Peters
authors.affiliation: Department of Molecular and Medical Virology, Ruhr-University, Bochum, Germany. Electronic address: Matthias.Tenbusch@rub.de.
authors.forename: M
authors.initials: M
authors.lastname: Tenbusch
mesh_terms: D000256:Adenoviridae / Q000235:genetics*; D000485:Allergens / Q000235:genetics / Q000276:immunology*; D000818:Animals; D015703:Antigens, CD / Q000276:immunology*; D001249:Asthma / Q000276:immunology / Q000517:prevention & control*; D016207:Cytokines / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology; D004195:Disease Models, Animal; D005260:Female; D057809:HEK293 Cells; D006801:Humans; D007114:Immunization / Q000379:methods*; D007073:Immunoglobulin E / Q000276:immunology; D037181:Lectins, C-Type / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D015778:Minor Histocompatibility Antigens / Q000276:immunology*; D010047:Ovalbumin / Q000235:genetics / Q000276:immunology*; D011956:Receptors, Cell Surface / Q000276:immunology*; D057127:Single-Chain Antibodies / Q000235:genetics / Q000276:immunology*
chemical_list: D000485:Allergens; D015703:Antigens, CD; D016207:Cytokines; C093569:DEC-205 receptor; D037181:Lectins, C-Type; D015778:Minor Histocompatibility Antigens; D011956:Receptors, Cell Surface; D057127:Single-Chain Antibodies; D007073:Immunoglobulin E; D010047:Ovalbumin
keywords: Adenoviral vectors; Allergic asthma; DC-targeting; DEC-205; Immunotherapy; Mucosa