title: Development and evaluation of a sublingual tablet based on recombinant Bet v 1 in birch pollen-allergic patients.
abstract: BACKGROUND
  Sublingual immunotherapy (SLIT) applied to type I respiratory allergies is commonly performed with natural allergen extracts. Herein, we developed a sublingual tablet made of pharmaceutical-grade recombinant Bet v 1.0101 (rBet v 1) and investigated its clinical safety and efficacy in birch pollen (BP)-allergic patients.
  
  
  METHODS
  Following expression in Escherichia coli and purification, rBet v 1 was characterized using chromatography, capillary electrophoresis, circular dichroism, mass spectrometry and crystallography. Safety and efficacy of rBet v 1 formulated as a sublingual tablet were assessed in a multicentre, double-blind, placebo-controlled study conducted in 483 patients with BP-induced rhinoconjunctivitis.
  
  
  RESULTS
  In-depth characterization confirmed the intact product structure and high purity of GMP-grade rBet v 1. The crystal structure resolved at 1.2 Å documented the natural conformation of the molecule. Native or oxidized forms of rBet v 1 did not induce the production of any proinflammatory cytokine by blood dendritic cells or mononuclear cells. Bet v 1 tablets were well tolerated by patients, consistent with the known safety profile of SLIT. The average adjusted symptom scores were significantly decreased relative to placebo in patients receiving once daily for 5 months rBet v 1 tablets, with a mean difference of 17.0-17.7% relative to the group treated with placebo (P < 0.025), without any influence of the dose in the range (12.5-50 μg) tested.
  
  
  CONCLUSIONS
  Recombinant Bet v 1 has been produced as a well-characterized pharmaceutical-grade biological drug. Sublingual administration of rBet v 1 tablets is safe and efficacious in patients with BP allergic rhinoconjunctivitis.
authors.affiliation: Stallergenes, Antony, France.
authors.forename: E
authors.initials: E
authors.lastname: Nony
authors.affiliation: Stallergenes, Antony, France.
authors.forename: J
authors.initials: J
authors.lastname: Bouley
authors.affiliation: Stallergenes, Antony, France.
authors.forename: M
authors.initials: M
authors.lastname: Le Mignon
authors.affiliation: Stallergenes, Antony, France.
authors.forename: P
authors.initials: P
authors.lastname: Lemoine
authors.affiliation: Stallergenes, Antony, France.
authors.forename: K
authors.initials: K
authors.lastname: Jain
authors.affiliation: Stallergenes, Antony, France.
authors.forename: S
authors.initials: S
authors.lastname: Horiot
authors.affiliation: Stallergenes, Antony, France.
authors.forename: L
authors.initials: L
authors.lastname: Mascarell
authors.affiliation: UFR Pharmacie Paris 11, Châtenay-Malabry, France.
authors.forename: M
authors.initials: M
authors.lastname: Pallardy
authors.affiliation: Structural Immunology, AFMB-UMR7257, Marseille, France.
authors.forename: R
authors.initials: R
authors.lastname: Vincentelli
authors.affiliation: Structural Immunology, AFMB-UMR7257, Marseille, France.
authors.forename: P
authors.initials: P
authors.lastname: Leone
authors.affiliation: Structural Immunology, AFMB-UMR7257, Marseille, France.
authors.forename: A
authors.initials: A
authors.lastname: Roussel
authors.affiliation: Stallergenes, Antony, France.
authors.forename: T
authors.initials: T
authors.lastname: Batard
authors.affiliation: Stallergenes, Antony, France.
authors.forename: K
authors.initials: K
authors.lastname: Abiteboul
authors.affiliation: Stallergenes, Antony, France.
authors.forename: B
authors.initials: B
authors.lastname: Robin
authors.affiliation: Stallergenes, Antony, France.
authors.forename: O
authors.initials: O
authors.lastname: de Beaumont
authors.affiliation: Department of Respiratory Medicine and Allergology, Sahlgrenska University Hospital, Goteborg, Sweden.
authors.forename: M
authors.initials: M
authors.lastname: Arvidsson
authors.affiliation: Department of Respiratory Medicine and Allergology, Sahlgrenska University Hospital, Goteborg, Sweden.
authors.forename: S
authors.initials: S
authors.lastname: Rak
authors.affiliation: Stallergenes, Antony, France.
authors.forename: P
authors.initials: P
authors.lastname: Moingeon
mesh_terms: D000293:Adolescent; D000328:Adult; D000485:Allergens / Q000737:chemistry / Q000235:genetics / Q000276:immunology* / Q000302:isolation & purification; D052179:Antigens, Plant / Q000737:chemistry / Q000235:genetics / Q000276:immunology* / Q000302:isolation & purification; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008958:Models, Molecular; D011058:Pollen / Q000276:immunology*; D011487:Protein Conformation; D011994:Recombinant Proteins; D012129:Respiratory Function Tests; D006255:Rhinitis, Allergic, Seasonal / Q000175:diagnosis / Q000276:immunology* / Q000628:therapy*; D012307:Risk Factors; D063729:Sublingual Immunotherapy / Q000009:adverse effects; D055815:Young Adult
chemical_list: D000485:Allergens; D052179:Antigens, Plant; D011994:Recombinant Proteins; C061312:Bet v 1 allergen, Betula
keywords: Bet v 1; birch pollen; recombinant allergen; sublingual immunotherapy