Development and evaluation of a sublingual tablet based on recombinant Bet v 1 in birch pollen‐allergic patients

E. Nony; J. Bouley; M. Le Mignon; P. LEMOINE; K. Jain; S. Horiot; L. Mascarell; M. Pallardy; R. Vincentelli; P. Leone; A. Roussel; T. Batard; K. Abiteboul; B. Robin; O. De Beaumont; M. Arvidsson; S. Rak; P. Moingeon

doi:10.1111/all.12622

journal article Apr 20, 2015

Development and evaluation of a sublingual tablet based on recombinant Bet v 1 in birch pollen‐allergic patients

E. Nony J. Bouley M. Le Mignon P. LEMOINE K. Jain S. Horiot L. Mascarell M. Pallardy R. Vincentelli P. Leone A. Roussel T. Batard K. Abiteboul B. Robin O. De Beaumont M. Arvidsson S. Rak P. Moingeon

Allergy Vol. 70 No. 7 pp. 795-804 · Wiley

View at Publisher Save 10.1111/all.12622

Abstract

AbstractBackgroundSublingual 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.MethodsFollowing 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.ResultsIn‐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.ConclusionRecombinant 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.

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Details

Published: Apr 20, 2015
Vol/Issue: 70(7)
Pages: 795-804
License: View

Authors

E

E. Nony

Stallergenes Antony France

J

J. Bouley

Stallergenes Antony France

M

M. Le Mignon

Stallergenes Antony France

P

P. LEMOINE

Stallergenes Antony France

K

K. Jain

Stallergenes Antony France

S

S. Horiot

Stallergenes Antony France

L

L. Mascarell

Stallergenes Antony France

M

M. Pallardy

UFR Pharmacie Paris 11 Châtenay‐Malabry France

R

R. Vincentelli

Structural Immunology AFMB‐UMR7257 Marseille France

P

P. Leone

Structural Immunology AFMB‐UMR7257 Marseille France

A

A. Roussel

Structural Immunology AFMB‐UMR7257 Marseille France

T

T. Batard

Stallergenes Antony France

K

K. Abiteboul

Stallergenes Antony France

B

B. Robin

Stallergenes Antony France

O

O. De Beaumont

Stallergenes Antony France

M

M. Arvidsson

Department of Respiratory Medicine and Allergology Sahlgrenska University Hospital Goteborg Sweden

S

S. Rak

Department of Respiratory Medicine and Allergology Sahlgrenska University Hospital Goteborg Sweden

P

P. Moingeon

Stallergenes Antony France

Funding

Stallergenes

Cite This Article

E. Nony, J. Bouley, M. Le Mignon, et al. (2015). Development and evaluation of a sublingual tablet based on recombinant Bet v 1 in birch pollen‐allergic patients. Allergy, 70(7), 795-804. https://doi.org/10.1111/all.12622

Development and evaluation of a sublingual tablet based on recombinant Bet v 1 in birch pollen‐allergic patients

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