Skin test evaluation of genetically engineered hypoallergenic derivatives of the major birch pollen allergen, Bet v 1:: Results obtained with a mix of two recombinant Bet v 1 fragments and recombinant Bet v 1 trimer in a Swedish population before the birch pollen season

Background: More than 95% of birch pollen-allergic subjects react with the major birch pollen allergen, Bet v 1, and almost 60% of them are sensitized exclusively to this allergen. Objective: The aim of this study was to compare the in vivo biologic activity of genetically engineered hypoallergenic derivatives of Bet v 1 (an equimolar mixture of 2 recombinant [r] Bet v 1 fragments and of rBet v I trimer) with that of rBet v 1 wild-type by skin prick and intradermal testing. Methods: Birch pollen-allergic patients who had not received immunotherapy (n = 23), a group of allergic patients without birch pollen allergy (n = 12), and nonatopic persons (n = 8) from northern Europe (Sweden) underwent skin prick and intradermal testing with different concentrations of the recombinant allergens and commercial birch pollen extract before the birch pollen season. Immediate and late-phase reactions were recorded and allergen-specific IgE and IgG subclass responses were determined by CAP radioallergosorbent test and ELISA, respectively. Results: Atopic persons without birch pollen allergy and nonatopic individuals did not have skin reactions to rBet v 1 wild-type and genetically engineered hypoallergenic derivatives, By intradermal testing, 8 of 23 and 13 of 23 birch pollen-allergic patients did not react with the highest concentration (1 mu g/mL) of the rBet v 1 fragment mix and rBet v 1 trimer, respectively, compared with 1 with rBet v 1 wild type. Likewise, the highest concentration (100 mu g/mL) of fragment mix or trimer failed to elicit a positive skin prick test in 18 of 23 and 15 of 23 patients in comparison with 0/23 with the monomer. No late reactions were observed. Conclusion: The recombinant hypoallergenic birch pollen allergens can probably be used for patient-tailored immunotherapy with a reduced risk to induce anaphylactic reactions.