Premium
Development and evaluation of a sublingual tablet based on recombinant Bet v 1 in birch pollen‐allergic patients
Author(s) -
y E.,
Bouley J.,
Le Mig M.,
Lemoine P.,
Jain K.,
Horiot S.,
Mascarell L.,
Pallardy M.,
Vincentelli R.,
Leone P.,
Roussel A.,
Batard T.,
Abiteboul K.,
Robin B.,
Beaumont O.,
Arvidsson M.,
Rak S.,
Moingeon P.
Publication year - 2015
Publication title -
allergy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.363
H-Index - 173
eISSN - 1398-9995
pISSN - 0105-4538
DOI - 10.1111/all.12622
Subject(s) - sublingual administration , medicine , placebo , allergen , sublingual immunotherapy , allergy , recombinant dna , slit , chromatography , immunology , pharmacology , chemistry , pathology , biology , biochemistry , alternative medicine , gene , genetics
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 B et v 1.0101 (r B et v 1) and investigated its clinical safety and efficacy in birch pollen ( BP )‐allergic patients. Methods Following expression in E scherichia coli and purification, r B et v 1 was characterized using chromatography, capillary electrophoresis, circular dichroism, mass spectrometry and crystallography. Safety and efficacy of r B et 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 r B et v 1. The crystal structure resolved at 1.2 Å documented the natural conformation of the molecule. Native or oxidized forms of r B et 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 rB et 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. Conclusion Recombinant B et v 1 has been produced as a well‐characterized pharmaceutical‐grade biological drug. Sublingual administration of r B et v 1 tablets is safe and efficacious in patients with BP allergic rhinoconjunctivitis.