title: Evaluation of therapeutic sublingual vaccines in a murine model of chronic house dust mite allergic airway inflammation.
abstract: BACKGROUND
  Second generation therapeutic vaccines based upon recombinant allergens or natural extracts, potentially formulated in vector systems or adjuvants, are being developed. To this aim, preclinical studies in relevant animal models are needed to select proper allergens, formulations and administration schemes.
  
  
  OBJECTIVE
  To develop a chronic house dust mite (HDM) allergy model to evaluate sublingual therapeutic vaccine candidates.
  
  
  METHODS
  The BABL/c mice that were used were sensitized with Dermatophagoides pteronyssinus (Dpte) and Dermatophagoides farinae (Dfar) mite extracts by intraperitoneal injections followed by aerosol exposures. Animals subsequently underwent sublingual immunotherapy (SLIT) with either Dpte, Dfar or Dpte/Dfar extracts, twice a week for 8 weeks. SLIT efficacy was assessed by whole body plethysmography, lung histology and broncho-alveolar lavages cell counts. Specific T cell and antibody responses to major and minor HDM allergens were monitored in tissues and serum/saliva, respectively.
  
  
  RESULTS
  Mice sensitized to Dpte and Dfar allergens exhibited strong airway hyperresponsiveness (AHR) and lung inflammatory infiltrates including eosinophils. Sensitized animals mounted Th2-biased cellular and humoral responses specific for group 1 and 2 major allergens, as well as group 5, 7 and 10 minor allergens. This phenotype was sustained for at least 2 months, allowing the evaluation of immunotherapeutic protocols with HDM extracts-based vaccines. In this model, SLIT decreased AHR and Th2 responses and induced HDM-specific IgAs in saliva. The Dpte/Dfar mix proved the most efficacious when compared to Dpte or Dfar extracts alone.
  
  
  CONCLUSIONS
  The efficacy of a sublingual vaccine based on a Dpte/Dfar allergen extract mix was demonstrated in a well standardized murine model of chronic allergic airway inflammation based on clinically relevant mite allergens. The latter will be used as a benchmark for evaluation of future vaccines, including recombinant allergens. This HDM allergic airway inflammation animal model is a useful tool to design and select candidate vaccines to be tested in humans.
authors.affiliation: Research and Development, Stallergenes SA, Antony, France.
authors.forename: S
authors.initials: S
authors.lastname: Tourdot
authors.forename: S
authors.initials: S
authors.lastname: Airouche
authors.forename: N
authors.initials: N
authors.lastname: Berjont
authors.forename: A
authors.initials: A
authors.lastname: Da Silveira
authors.forename: L
authors.initials: L
authors.lastname: Mascarell
authors.forename: A
authors.initials: A
authors.lastname: Jacquet
authors.forename: L
authors.initials: L
authors.lastname: Caplier
authors.forename: M
authors.initials: M
authors.lastname: Langelot
authors.forename: V
authors.initials: V
authors.lastname: Baron-Bodo
authors.forename: P
authors.initials: P
authors.lastname: Moingeon
mesh_terms: D000286:Administration, Sublingual; D000818:Animals; D039741:Antigens, Dermatophagoides / Q000008:administration & dosage / Q000276:immunology*; D016535:Bronchial Hyperreactivity / Q000276:immunology* / Q000517:prevention & control / Q000628:therapy*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D003888:Desensitization, Immunologic; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D007249:Inflammation / Q000276:immunology / Q000628:therapy; D051379:Mice; D008807:Mice, Inbred BALB C; D039981:Pyroglyphidae / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology; D014612:Vaccines / Q000276:immunology
chemical_list: D039741:Antigens, Dermatophagoides; D014612:Vaccines