BackgroundBet v 1, the major allergen in birch pollen, is recognized by more than 90% of patients allergic to birch in northern and central Europe. Immunotherapy is commonly performed with birch pollen extracts. Recently, hypoallergenic derivatives of Bet v 1 (rBet v 1 fragments, rBet v 1 dimer and trimer) were constructed and purified.ObjectiveOur aim was to compare the allergenic activity of wild‐type rBet v 1 with recombinant Bet v 1 derivatives (rBet v 1 fragments, dimer and trimer) with potentially reduced anaphylactic activity by skin testing in a French population.MethodsAmong the 36 birch pollen allergic patients included in the study, 29 were tested by skin prick testing and 30 by intradermal injections with purified monosubstances: rBet v 1 fragments (F1: aa1–74 and F2: aa75–160), Bet v 1 dimer and trimer. Intradermal tests were performed by the end‐point intradermal titration method. Eight of the intradermally‐tested patients were previously hyposensitized. Tests were performed over a period of 6 months (before, during and after birch pollen season); Bet v 1‐specific IgE and IgG4 subclass responses were measured by immunoblotting and ELISA.ResultsAll patients showed lower reactivity with the modified rBet v 1 allergens, both in skin prick and intradermal tests. In 25 and 23 out of 29 patients the lowest concentration of fragment 1 and 2, respectively, resulting in a positive prick test was 100‐fold higher than the lowest concentration of monomer resulting in a positive prick test. For dimer it was 100‐fold or more in 25 out of 29 patients, and for trimer it was 100‐fold or superior in 26 out of 29 patients. By intradermal testing, the end‐point concentration was 160‐fold higher for trimer than for monomer in 24 patients and 40‐fold higher in five patients. For the two fragments the end‐point concentration was 160‐fold higher in 20 out of 22 patients.ConclusionGenetically modified hypoallergenic derivatives of the major birch pollen allergen, Bet v 1 showed reduced capacity to induce immediate type skin reactions. They may represent candidate molecules for immunotherapy of birch pollen allergy with reduced risk of anaphylactic side‐effects.

Pauli, Purohit, Oster, De Blay, Vrtala, Niederberger, Kraft, & Valenta. (2000). Comparison of genetically engineered hypoallergenic rBet v 1 derivatives with rBet v 1 wild‐type by skin prick and intradermal testing: results obtained in a French population. Clinical & Experimental Allergy, 30(8), 1076–1084. Portico.