Mucosal expression of DEC-205 targeted allergen alleviates an asthmatic phenotype in mice

JOURNAL OF CONTROLLED RELEASE

卷:237

Article

Maaske, A.¹  Devos, F. C.²  Niezold, T.^1,5  Lapuente, D.¹  Tannapfel, A.³  Vanoirbeek, J. A.²  Ueberla, K.^1,6  Peters, M.⁴  Tenbusch, M.¹ 

[1] Ruhr Univ Bochum, Dept Mol & Med Virol, Univ Str 150, D-44801 Bochum, Germany

[2] Katholieke Univ Leuven, Ctr Environm & Hlth, Dept Publ Hlth & Primary Care, Leuven, Belgium

[3] Ruhr Univ Bochum, Inst Pathol, Bochum, Germany

[4] Ruhr Univ Bochum, Dept Expt Pneumol, Bochum, Germany

[5] NIAID, Biodefense Res Sect, Vaccine Res Ctr, NIH, Bethesda, MD 20814 USA

[6] Univ Erlangen Nurnberg, Univ Klinikum Erlangen, Inst Clin & Mol Virol, Erlangen, Germany

关键词: Allergic asthma;    DC-targeting;    DEC-205;    Adenoviral vectors;    Immunotherapy;    Mucosa;   

DOI  :  10.1016/j.jconrel.2016.06.043

来源: Elsevier

【 摘 要 】

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. (C) 2016 The Authors. Published by Elsevier B.V.

【 授权许可】

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