title: Double-blind, placebo-controlled, dose-ranging study of new recombinant hypoallergenic Bet v 1 in an environmental exposure chamber.
abstract: BACKGROUND
  Recombinant allergens offer a tool for improving specific immunotherapy (SIT).
  
  
  OBJECTIVE
  To find the optimal dose of a new hypoallergenic folding variant of recombinant Bet v 1 (rBet v 1-FV) as SIT for patients with birch pollen allergy.
  
  
  METHODS
  Before SIT, thirty-seven adult patients were exposed for eight hours in an environmental exposure chamber (EEC) to birch pollen at an average concentration of 3500 ± 500 grains/m(3) , then randomized to four maintenance dose groups of rBet v 1-FV and one placebo group: 20 μg (n = 7), 80 μg (n = 8), 160 μg (n = 7), 320 μg (n = 8), and placebo (n = 7). Patients were treated for 10 weeks with weekly injections and then re-exposed in the EEC. The optimal dose for SIT was assessed using efficacy results from the EEC, IgG responses, and tolerability.
  
  
  RESULTS
  Thirty-six patients were evaluable for efficacy assessment. The total symptom score significantly decreased in all active groups compared with placebo (-18.8% for placebo patients; -71.9%, P = 0.0022 for 20 μg; -75.6%, P = 0.0007 for 80 μg; -81.8%, P = 0.0009 for 160 μg; -78.3%, P = 0.0003 for 320 μg). IgG1 increased significantly in all active groups compared to placebo. All four active doses were well tolerated, no serious adverse event occurred; two Grade II reactions, according to EAACI classification, were observed, one in each of the 160- and 320-μg groups.
  
  
  CONCLUSIONS
  Considering efficacy, immunological response, and tolerability, a maintenance dose of 80 μg of rBet v 1-FV appears to be the ideal dose for allergen immunotherapy in birch pollen allergic patients.
authors.affiliation: Medical Department Allergopharma GmbH & Co. KG, Reinbek, Germany.
authors.forename: W
authors.initials: W
authors.lastname: Meyer
authors.forename: A
authors.initials: A
authors.lastname: Narkus
authors.forename: A M
authors.initials: AM
authors.lastname: Salapatek
authors.forename: D
authors.initials: D
authors.lastname: Häfner
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000485:Allergens / Q000008:administration & dosage* / Q000627:therapeutic use; D000704:Analysis of Variance; D052179:Antigens, Plant / Q000008:administration & dosage* / Q000627:therapeutic use; D001273:Atmosphere Exposure Chambers; D003888:Desensitization, Immunologic / Q000295:instrumentation / Q000379:methods*; D004306:Dose-Response Relationship, Immunologic; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D016018:Least-Squares Analysis; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000627:therapeutic use; D006255:Rhinitis, Allergic, Seasonal / Q000276:immunology / Q000628:therapy*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000485:Allergens; D052179:Antigens, Plant; D011994:Recombinant Proteins; C061312:Bet v 1 allergen, Betula