title: Epicutaneous immunotherapy with a hypoallergenic Bet v 1 suppresses allergic asthma in a murine model.
abstract: BACKGROUND
  Due to reduced allergic potency, hypoallergenic variants have been suggested as safer and potentially more efficacious alternative to the corresponding wild-type allergens in allergen-specific immunotherapy. Here, we aimed at investigating the efficacy of recombinant Bet v 1B2, a hypoallergenic folding variant of Bet v 1, in epicutaneous immunotherapy to suppress asthmatic features using a murine model of birch pollen allergy.
  
  
  RESULTS
  Before, or after sensitization with rBet v 1 plus ALUMW and intranasal challenges with birch pollen extract, BALB/c mice received epicutaneous immunization (EPI) with rBet v 1, or rBet v 1B2 on their depilated back. Prophylactic EPI with rBet v 1B2, but not with rBet v 1, suppressed serum levels of Bet v 1-specific IgE antibodies and reduced the number of eosinophils and the concentrations of Th2 cytokines in bronchoalveolar lavage. In an established allergic condition, serum levels of Bet v 1-specific IgE antibodies were similar between PBS-treated control mice and EPI-treated mice. However, therapeutic EPI with rBet v 1B2, but not with rBet v 1, significantly suppressed the development of airway inflammation and lung function impairment.
  
  
  CONCLUSIONS
  This study is the first to show the effect of therapeutic EPI with a recombinant form of a hypoallergenic folding variant on the suppression of asthmatic features. Our results suggest that rBet v 1B2 along with its reduced IgE-binding capacity could be a preferred therapeutic allergen than wild-type rBet v 1 in epicutaneous immunotherapy of birch pollen-induced allergic asthma, in particular due to a lower risk of allergic side effect.
authors: Junior Research Group 1 'Experimental Allergy Models', Paul-Ehrlich-Institut, Langen, Germany.
authors: S
authors: S
authors: Siebeneicher
authors: The III Medical Department, University Medical Centre, Mainz, Germany.|Experimental Asthma Research, Research Center Borstel, Leibniz-Center for Medicine and Biosciences, Borstel, Germany.
authors: S
authors: S
authors: Reuter
authors: Vice President's Research Group 'Molecular Allergology', Paul-Ehrlich-Institut, Langen, Germany.
authors: A
authors: A
authors: Wangorsch
authors: Junior Research Group 1 'Experimental Allergy Models', Paul-Ehrlich-Institut, Langen, Germany.|Vice President's Research Group 'Molecular Allergology', Paul-Ehrlich-Institut, Langen, Germany.
authors: M
authors: M
authors: Krause
authors: Division of Allergology, Paul-Ehrlich-Institut, Langen, Germany.
authors: K
authors: K
authors: Foetisch
authors: The III Medical Department, University Medical Centre, Mainz, Germany.
authors: A
authors: A
authors: Heinz
authors: Department of Quality Assurance and Radiological Protection, The National Institute of Infectious Diseases, Tokyo, Japan.
authors: S
authors: S
authors: Naito
authors: Division of Allergology, Paul-Ehrlich-Institut, Langen, Germany.
authors: A
authors: A
authors: Reuter
authors: Department of Pulmonology, Leiden University Medical Center, Leiden, the Netherlands.
authors: C
authors: C
authors: Taube
authors: Vice President's Research Group 'Molecular Allergology', Paul-Ehrlich-Institut, Langen, Germany.|Division of Allergology, Paul-Ehrlich-Institut, Langen, Germany.
authors: S
authors: S
authors: Vieths
authors: Vice President's Research Group 'Molecular Allergology', Paul-Ehrlich-Institut, Langen, Germany.|Division of Allergology, Paul-Ehrlich-Institut, Langen, Germany.
authors: S
authors: S
authors: Scheurer
authors: Junior Research Group 1 'Experimental Allergy Models', Paul-Ehrlich-Institut, Langen, Germany.|Vice President's Research Group 'Molecular Allergology', Paul-Ehrlich-Institut, Langen, Germany.
authors: M
authors: M
authors: Toda
mesh_terms: D000485:Allergens / Q000737:chemistry / Q000276:immunology; D000818:Animals; D052179:Antigens, Plant / Q000737:chemistry* / Q000276:immunology*; D001249:Asthma / Q000276:immunology / Q000517:prevention & control*; D003888:Desensitization, Immunologic / Q000379:methods*; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D015151:Immunoblotting; D051379:Mice; D008807:Mice, Inbred BALB C; D020033:Protein Isoforms / Q000276:immunology; D011994:Recombinant Proteins / Q000276:immunology; D012130:Respiratory Hypersensitivity / Q000276:immunology / Q000517:prevention & control*; D006255:Rhinitis, Allergic, Seasonal / Q000276:immunology / Q000517:prevention & control
chemical_list: D000485:Allergens; D052179:Antigens, Plant; D020033:Protein Isoforms; D011994:Recombinant Proteins; C061312:Bet v 1 allergen, Betula
keywords: birch pollen allergy; epicutaneous immunization; hypoallergen