title: Allergenicity, immunogenicity and dose-relationship of three intact allergen vaccines and four allergoid vaccines for subcutaneous grass pollen immunotherapy.
abstract: Different vaccines containing intact allergens or chemically modified allergoids as active ingredients are commercially available for specific immunotherapy. Allergoids are claimed to have decreased allergenicity without loss of immunogenicity and this is stated to allow administration of high allergoid doses. We compared the allergenicity and immunogenicity of four commercially available chemically modified grass pollen allergoid products with three commercially available intact grass pollen allergen vaccines. The allergenicity was investigated with immunoglobulin (Ig)E-inhibition and basophil activation assays. Human T cell proliferation and specific IgG-titres following mouse immunizations were used to address immunogenicity. Furthermore, intact allergen vaccines with different contents of active ingredients were selected to study the influence of the allergen dose. In general, a lower allergenicity for allergen vaccines was clearly linked to a reduced immunogenicity. Compared with the vaccine with the highest amount of intact allergen, the allergoids caused reduced basophil activation as well as diminished immunogenicity demonstrated by reduced T cell activation and/or reduced induction of murine grass-specific IgG antibodies. Interestingly, intact allergen vaccines with lower content of active ingredient exhibited similarly reduced allergenicity, while immunogenicity was still higher or equal to that of allergoids. The low allergenicity observed for some allergoids was inherently linked to a significantly lower immunogenic response questioning the rationale behind the chemical modification into allergoids. In addition, the linkage between allergenicity, immunogenicity and dose found for intact allergen vaccines and the immunogen as well as allergenic immune responses observed for allergoids suggest that the modified allergen vaccines do not contain high doses of immunologically active ingredients.
authors.affiliation: ALK-Abelló A/S, Research Department, Hørsholm, Denmark. hhn@dk.alk-abello.com
authors.forename: H
authors.initials: H
authors.lastname: Henmar
authors.forename: G
authors.initials: G
authors.lastname: Lund
authors.forename: L
authors.initials: L
authors.lastname: Lund
authors.forename: A
authors.initials: A
authors.lastname: Petersen
authors.forename: P A
authors.initials: PA
authors.lastname: Würtzen
mesh_terms: D000485:Allergens / Q000187:drug effects / Q000276:immunology*; D000080384:Allergoids; D000818:Animals; D001491:Basophils / Q000276:immunology; D004305:Dose-Response Relationship, Drug; D004306:Dose-Response Relationship, Immunologic; D006801:Humans; D007073:Immunoglobulin E / Q000378:metabolism; D007074:Immunoglobulin G / Q000378:metabolism; D007167:Immunotherapy / Q000379:methods; D051379:Mice; D008807:Mice, Inbred BALB C; D010936:Plant Extracts; D006109:Poaceae / Q000187:drug effects / Q000276:immunology*; D011058:Pollen / Q000187:drug effects / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology; D014612:Vaccines / Q000276:immunology* / Q000494:pharmacology
chemical_list: D000485:Allergens; D000080384:Allergoids; D007074:Immunoglobulin G; D010936:Plant Extracts; D014612:Vaccines; D007073:Immunoglobulin E