Double-blind, placebo-controlled, dose-ranging study of new recombinant hypoallergenic Bet v 1 in an environmental exposure chamber

Background Recombinant allergens offer a tool for improving specific immunotherapy (SIT). Objective To find the optimal dose of a new hypoallergenic folding variant of recombinant Bet v 1 (rBet v 1-FV) as SIT for patients with birch pollen allergy. Methods Before SIT, thirty-seven adult patients were exposed for eight hours in an environmental exposure chamber (EEC) to birch pollen at an average concentration of 3500 +/- 500grains/m3, then randomized to four maintenance dose groups of rBet v 1-FV and one placebo group: 20g (n=7), 80g (n=8), 160g (n=7), 320g (n=8), and placebo (n=7). Patients were treated for 10weeks with weekly injections and then re-exposed in the EEC. The optimal dose for SIT was assessed using efficacy results from the EEC, IgG responses, and tolerability. Results Thirty-six patients were evaluable for efficacy assessment. The total symptom score significantly decreased in all active groups compared with placebo (18.8% for placebo patients; 71.9%, P=0.0022 for 20g; 75.6%, P=0.0007 for 80g; 81.8%, P=0.0009 for 160g; 78.3%, P=0.0003 for 320g). IgG1 increased significantly in all active groups compared to placebo. All four active doses were well tolerated, no serious adverse event occurred; two Grade II reactions, according to EAACI classification, were observed, one in each of the 160- and 320-g groups. Conclusions Considering efficacy, immunological response, and tolerability, a maintenance dose of 80g of rBet v 1-FV appears to be the ideal dose for allergen immunotherapy in birch pollen allergic patients.