title: Epicutaneous immune modulation with Bet v 1 plus R848 suppresses allergic asthma in a murine model.
abstract: BACKGROUND
  Combining allergen(s) with an adjuvant is a strategy to improve the efficacy and safety of allergen-specific immunotherapy. Here, we aimed at investigating the adjuvant effects of polyadenylic-polyuridylic acid (poly(A:U)), a TLR3 agonist, and R848 (resiquimod), a TLR7 agonist, in epicutaneous immunotherapy with Bet v 1, the major birch pollen allergen, to intervene in birch pollen allergy.
  
  
  RESULTS
  BALB/c mice received epicutaneous immunization (EPI) with recombinant Bet v 1 (rBet v 1) alone, or plus poly(A:U), or R848 on their depilated back using patches. Among the groups, EPI with rBet v 1 and R848 induced detectable levels of IFN-γ-producing CD4(+) T cells in lymph nodes and Bet v 1-specific IgG2a antibodies in the sera of mice. Before or after EPI, mice were sensitized with rBet v 1 plus aluminium hydroxide adjuvant and intranasally challenged with birch pollen extract. Prophylactic EPI with rBet v 1 plus R848 inhibited the production of biologically active Bet v 1-specific IgE antibodies in sensitization. Prophylactic and therapeutic EPI with rBet v 1 plus R848 suppressed lung inflammation upon challenges. Remarkably, only rBet v 1 plus R848 reduced the development of enhanced pause (PenH), a substituted parameter for airway hyper-reactivity, in challenged mice. In contrast to R848, poly(A:U) did not present adjuvant effect on the suppression of asthmatic features.
  
  
  CONCLUSIONS
  Epicutaneous immunization with rBet v 1 plus R848 induced predominant Bet v 1-specific Th1 responses and efficiently suppressed asthmatic features elicited by birch pollen. R848 could be a promising adjuvant in epicutaneous immunotherapy for birch pollen-induced allergic asthma.
authors: Junior Research Group 1 'Experimental Allergy Models', Paul-Ehrlich-Institut, Langen, Germany.
authors: S
authors: S
authors: Siebeneicher
authors: S
authors: S
authors: Reuter
authors: M
authors: M
authors: Krause
authors: A
authors: A
authors: Wangorsch
authors: J
authors: J
authors: Maxeiner
authors: S
authors: S
authors: Wolfheimer
authors: S
authors: S
authors: Schülke
authors: S
authors: S
authors: Naito
authors: A
authors: A
authors: Heinz
authors: C
authors: C
authors: Taube
authors: S
authors: S
authors: Vieths
authors: S
authors: S
authors: Scheurer
authors: M
authors: M
authors: Toda
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D052179:Antigens, Plant / Q000008:administration & dosage* / Q000276:immunology*; D001249:Asthma / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D003888:Desensitization, Immunologic; D004195:Disease Models, Animal; D005260:Female; D007093:Imidazoles / Q000008:administration & dosage*; D007114:Immunization; D007073:Immunoglobulin E / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology; D051379:Mice; D011292:Premedication; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism
chemical_list: D052179:Antigens, Plant; D007093:Imidazoles; D007074:Immunoglobulin G; D011994:Recombinant Proteins; C061312:Bet v 1 allergen, Betula; D007073:Immunoglobulin E; C402365:resiquimod
keywords: R848; TLR7 agonist; adjuvant; birch pollen allergy; epicutaneous immunization