title: Efficacy of sublingual vectorized recombinant Bet v 1a in a mouse model of birch pollen allergic asthma.
abstract: BACKGROUND
  Second generation sublingual allergy vaccines based upon recombinant allergens combined with vector systems are being developed as an alternative to conventional allergen extracts. Herein, we evaluated the efficacy of a recombinant form of the major allergen Bet v 1a (rBet v 1a) formulated as a mucoadhesive particle in a preclinical model of birch pollen (BP) respiratory allergy.
  
  
  METHODS
  BALB/c mice were sensitized to BP extracts by intraperitoneal injections followed by aerosol exposures. Sensitized mice underwent sublingual immunotherapy (SLIT) twice a week for eight weeks with either a BP extract or rBet v 1a formulated in amylopectin-based microparticles (MPA). SLIT efficacy was assessed using whole body plethysmography, lung histology and cell counts in broncho-alveolar lavages (BAL) as read outs. BP and/or rBet v 1a-specific T cell and antibody responses were monitored in lung and serum, respectively. IgA levels were measured in saliva.
  
  
  RESULTS
  Mice sensitized to BP exhibit chronic airway hyperresponsiveness (AHR), lung inflammation (documented by compliance and resistance measurements), eosinophil infiltrates in BAL, as well as Bet v 1-specific Th2 biased responses. Both SLIT with soluble rBet v 1a (50μg/dose) and BP extract (equivalent to 50μg rBet v 1 per dose) lead to a significant reduction in AHR, lung eosinophilia and Th2 responses. A sub-optimal dose of 5μg of rBet v 1a displays a similar level of efficacy with a significant decrease of Th2 responses when formulated with MPA microparticles. In addition, allergen vectorization with mucoadhesive particles allows a faster reduction in AHR in sensitized animals.
  
  
  CONCLUSIONS
  We demonstrate in a murine model of chronic BP respiratory allergy the efficacy of SLIT with vectorized rBet v 1a. Thus, combining recombinant allergens with mucoadhesive vector systems paves the ground for improved second generation sublingual allergy vaccines.
authors.affiliation: Research and Development, Stallergenes SA, Antony, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Tourdot
authors.forename: Sabi
authors.initials: S
authors.lastname: Airouche
authors.forename: Nathalie
authors.initials: N
authors.lastname: Berjont
authors.forename: Hélène
authors.initials: H
authors.lastname: Moussu
authors.forename: Didier
authors.initials: D
authors.lastname: Betbeder
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Nony
authors.forename: Véronique
authors.initials: V
authors.lastname: Bordas-Le Floch
authors.forename: Véronique
authors.initials: V
authors.lastname: Baron-Bodo
authors.forename: Laurent
authors.initials: L
authors.lastname: Mascarell
authors.forename: Philippe
authors.initials: P
authors.lastname: Moingeon
mesh_terms: D000286:Administration, Sublingual; D000485:Allergens / Q000276:immunology; D000818:Animals; D052179:Antigens, Plant / Q000008:administration & dosage* / Q000276:immunology*; D001249:Asthma / Q000276:immunology / Q000517:prevention & control*; D029662:Betula / Q000276:immunology*; D016535:Bronchial Hyperreactivity / Q000276:immunology / Q000517:prevention & control; D004195:Disease Models, Animal; D005260:Female; D051379:Mice; D008807:Mice, Inbred BALB C; D011014:Pneumonia / Q000276:immunology / Q000517:prevention & control; D011058:Pollen / Q000276:immunology*; D011897:Random Allocation; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000276:immunology; D006255:Rhinitis, Allergic, Seasonal / Q000276:immunology / Q000517:prevention & control*; D018418:Th2 Cells / Q000276:immunology; D014612:Vaccines / Q000008:administration & dosage / Q000276:immunology
chemical_list: D000485:Allergens; D052179:Antigens, Plant; D011994:Recombinant Proteins; D014612:Vaccines; C061312:Bet v 1 allergen, Betula