Non-anaphylactic surface-exposed peptides of the major birch pollen allergen, Bet v 1, for preventive vaccination

Summary Background Almost 100 million allergic patients are sensitized to the major birch pollen allergen, Bet v 1, a 17 kDa protein containing most of the IgE epitopes present in pollens of trees belonging to the Fagales order and plant‐derived food. Objective Our aim was to develop an approach for the rational design of B cell epitope‐derived, non‐allergenic peptide allergy vaccines. Methods According to the three‐dimensional (3‐D) structure of birch pollen allergen, Bet v 1, six peptides comprising 25–32 preferably solvent‐exposed amino acids were synthesized. Results Because of lack of secondary structure, the peptides showed no allergenic activity in allergic patients. In a mouse model of birch pollen allergy, peptide vaccination induced Bet v 1‐specific IgG and prevented IgE‐mediated allergic sensitization to Bet v 1. The protective role of peptide‐induced blocking antibodies is demonstrated by inhibition of allergic patients IgE binding to the allergen and by blocking of allergen‐induced basophil degranulation. Conclusion Our results indicate the mechanistic importance of blocking antibodies for allergy vaccination and present a B cell epitope‐based approach for the rational design of safe peptide allergy vaccines whenever the structure of the disease‐eliciting allergen is known.