title: Prevention of birch pollen-related food allergy by mucosal treatment with multi-allergen-chimers in mice.
abstract: BACKGROUND
  Among birch pollen allergic patients up to 70% develop allergic reactions to Bet v 1-homologue food allergens such as Api g 1 (celery) or Dau c 1 (carrot), termed as birch pollen-related food allergy. In most cases, specific immunotherapy with birch pollen extracts does not reduce allergic symptoms to the homologue food allergens. We therefore genetically engineered a multi-allergen chimer and tested if mucosal treatment with this construct could represent a novel approach for prevention of birch pollen-related food allergy.
  
  
  METHODS
  BALB/c mice were poly-sensitized with a mixture of Bet v 1, Api g 1 and Dau c 1 followed by a sublingual challenge with carrot, celery and birch pollen extracts. For prevention of allergy sensitization an allergen chimer composed of immunodominant T cell epitopes of Api g 1 and Dau c 1 linked to the whole Bet v 1 allergen, was intranasally applied prior to sensitization.
  
  
  RESULTS
  Intranasal pretreatment with the allergen chimer led to significantly decreased antigen-specific IgE-dependent β-hexosaminidase release, but enhanced allergen-specific IgG2a and IgA antibodies. Accordingly, IL-4 levels in spleen cell cultures and IL-5 levels in restimulated spleen and cervical lymph node cell cultures were markedly reduced, while IFN-γ levels were increased. Immunomodulation was associated with increased IL-10, TGF-β and Foxp3 mRNA levels in NALT and Foxp3 in oral mucosal tissues. Treatment with anti-TGF-β, anti-IL10R or anti-CD25 antibodies abrogated the suppression of allergic responses induced by the chimer.
  
  
  CONCLUSIONS
  Our results indicate that mucosal application of the allergen chimer led to decreased Th2 immune responses against Bet v 1 and its homologue food allergens Api g 1 and Dau c 1 by regulatory and Th1-biased immune responses. These data suggest that mucosal treatment with a multi-allergen vaccine could be a promising treatment strategy to prevent birch pollen-related food allergy.
authors: Institute of Specific Prophylaxis and Tropical Medicine, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria.
authors: Elisabeth
authors: E
authors: Hoflehner
authors: Karin
authors: K
authors: Hufnagl
authors: Irma
authors: I
authors: Schabussova
authors: Joanna
authors: J
authors: Jasinska
authors: Karin
authors: K
authors: Hoffmann-Sommergruber
authors: Barbara
authors: B
authors: Bohle
authors: Rick M
authors: RM
authors: Maizels
authors: Ursula
authors: U
authors: Wiedermann
mesh_terms: D000281:Administration, Intranasal; D000485:Allergens / Q000276:immunology* / Q000494:pharmacology; D000818:Animals; D019138:Antibodies, Blocking / Q000494:pharmacology; D052179:Antigens, Plant / Q000276:immunology*; D001491:Basophils / Q000187:drug effects / Q000276:immunology / Q000502:physiology; D029662:Betula / Q000276:immunology*; D015550:Cell Degranulation / Q000187:drug effects; D016207:Cytokines / Q000096:biosynthesis; D000939:Epitopes / Q000276:immunology; D005260:Female; D005512:Food Hypersensitivity / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D005786:Gene Expression Regulation / Q000187:drug effects; D007111:Immunity, Cellular / Q000187:drug effects / Q000276:immunology; D056724:Immunity, Humoral / Q000187:drug effects / Q000276:immunology; D007114:Immunization; D007073:Immunoglobulin E / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D009297:Nasal Mucosa / Q000187:drug effects* / Q000276:immunology; D011058:Pollen / Q000276:immunology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000276:immunology / Q000494:pharmacology*; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology
chemical_list: D000485:Allergens; D019138:Antibodies, Blocking; D052179:Antigens, Plant; D016207:Cytokines; D000939:Epitopes; D012333:RNA, Messenger; D011994:Recombinant Proteins; D007073:Immunoglobulin E