B-cell epitope-based peptide allergy vaccines

Type I allergy, an IgE-mediated hypersensitivity disease, affects more than 25% of the population in industrialized countries. Allergen-specific immunotherapy, the only curative approach towards therapy of Type I allergy, suffers from several disadvantages. Currently used allergen extracts represent mixtures of allergenic and non-allergenic extracts which cannot be tailored according to the patients sensitization profile. Furthermore, administration of allergen extracts can cause severe side effects which may comprise the induction of immediate symptoms as well as late phase symptoms. Considerable progress has been made in the recent years in the field of molecular allergen characterization. cDNAs coding for many of the most important allergens have been isolated and recombinant allergens which assemble the epitope spectrum of natural allergens have been produced. Based on sequence and structural information of major allergens, this project proposes to explore the usefulness of B cell epitope-derived peptide allergy vaccines for the treatment of Type I allergy. Peptides derived from B cell epitopes of four allergens which belong to the most important elicitors of Type I allergy and comprise most of the relevant IgE epitopes of the corresponding allergen sources (i.e., the major birch pollen allergen, Bet v 1, the major timothy grass pollen allergen, Phl p 5 and the cat allergens, Fel d 1 and cat albumin) will be synthesized. The peptides will be selected by combining informations from sequence, structural and epitope analyses. The synthetic peptides will be characterized by physicochemical techniques regarding mass, identity and fold. Furthermore the peptides will be tested for the presence of IgE and T cell epitopes as well as for their allergenic activity by basophil histamine release tests. Peptides which in comparison to the wildtype allergens exhibit reduced or abolished allergenic activity in the skin of allergic patients will be tested for their capacity to induce protective antibody responses in animals. Finally it will be tested if peptide administration can prevent the induction of Type I allergy or ameliorate established Type I allergy in murine models. The B cell epitope-derived peptide allergy approach may contribute to the improvement of allergen-specific immunotherapy because it will allow to produce well defined peptide vaccines with reduced anaphylactic potential that can be used to treat allergic patients according to their sensitization profile.