title: An alternative allergen:adjuvant formulation potentiates the immunogenicity and reduces allergenicity of a novel subcutaneous immunotherapy product for treatment of grass-pollen allergy.
abstract: BACKGROUND
  Subcutaneous specific immunotherapy (SCIT) has proven sustained clinical efficacy against allergy. The recommended regimen for SCIT is a gradual updosing over a period of weeks. Commonly, in commercial products for SCIT, the specific allergen is formulated with an adjuvant, most often in the form of aluminium hydroxide (AlOH). It has been shown that allergen-specific IgG antibodies are induced as a result of successful SIT.
  
  
  OBJECTIVE
  To investigate the possibility of optimizing the formulation of AlOH-based grass-pollen allergy vaccines for SCIT in a way that allows for shorter updosing regimens while maintaining the immunogenicity of the vaccine.
  
  
  METHODS
  Mice were immunized with various concentrations of Phleum pratense (Phl p) allergen extract and AlOH or a fixed dilution of the maintenance doses of one conventional and one alternatively formulated vaccine. The kinetics of Phl p-specific IgG antibody responses in serum and spleen T cell responses were determined. Allergenicity, measured as the ability of the formulations to activate human basophils, was also determined. In addition, human T cell responses and the expression of dendritic cell surface markers after vaccine challenge in vitro were analysed.
  
  
  RESULTS
  Specific IgG antibody responses were shown to depend on the AlOH concentration, but not on the allergen concentrations. The immunogenicity of the conventional formulation and the alternative formulation was shown to be similar with regard to the in vivo-induced IgG and T cell responses. In contrast, the allergenicity of the alternative formulation was significantly reduced compared with the conventional formulation.
  
  
  CONCLUSIONS
  The optimization of the formulation allows for administration of a lower dose of allergen while maintaining the immunogenicity of the product and at the same time reducing allergenicity.
  
  
  CONCLUSIONS
  This study indicates that the optimization of the allergen and the adjuvant formulation could benefit the safety/efficacy profile and allow for shorter updosing.
authors.affiliation: Department of Pharmacology, ALK-Abelló A/S, Hoersholm, Denmark. crkdk@alk-abello.com
authors.forename: C
authors.initials: C
authors.lastname: Rask
authors.forename: L
authors.initials: L
authors.lastname: Lund
authors.forename: G
authors.initials: G
authors.lastname: Lund
authors.forename: B
authors.initials: B
authors.lastname: Heydenreich
authors.forename: P
authors.initials: P
authors.lastname: Wurtzen
authors.forename: I
authors.initials: I
authors.lastname: Bellinghausen
authors.forename: J
authors.initials: J
authors.lastname: Saloga
authors.forename: K
authors.initials: K
authors.lastname: Lund
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000485:Allergens / Q000008:administration & dosage / Q000276:immunology*; D000536:Aluminum Hydroxide / Q000276:immunology; D000818:Animals; D003888:Desensitization, Immunologic / Q000379:methods*; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D007279:Injections, Subcutaneous; D051379:Mice; D008807:Mice, Inbred BALB C; D031784:Phleum / Q000276:immunology; D010936:Plant Extracts / Q000008:administration & dosage / Q000276:immunology; D006109:Poaceae / Q000276:immunology*; D011058:Pollen / Q000276:immunology*; D006255:Rhinitis, Allergic, Seasonal / Q000276:immunology / Q000628:therapy*; D013601:T-Lymphocytes / Q000276:immunology; D016896:Treatment Outcome
chemical_list: D000276:Adjuvants, Immunologic; D000485:Allergens; D007074:Immunoglobulin G; D010936:Plant Extracts; D000536:Aluminum Hydroxide