Pre‐Seasonal Treatment With Recombinant Carrier‐Based Birch Vaccine Improves Birch Pollen Allergy

Background We have recently reported the preclinical characterization of a recombinant birch pollen allergy vaccine based on a fusion protein, AB ‐ PreS , consisting of allergen‐derived peptides fused to the hepatitis B virus ( HBV )‐derived PreS surface protein as immunological carrier. Objective To investigate in a clinical study the usefulness of the AB ‐ PreS vaccine, termed GNR ‐127, for allergen‐specific immunotherapy of birch pollen allergy. Methods Stage 1 of the study, an open‐label Phase I study, determined among three doses (20 μg: n = 6; 40 μg: n = 6; 80 μg: n = 6) administered as Aluminum‐hydroxide‐adsorbed vaccines subcutaneously five times in monthly intervals, the highest tolerated doses. In the following Stage 2, randomized patients (placebo: n = 45; 40 μg: n = 43; 80 μg: n = 44) received in a single‐blind, placebo‐controlled Phase II study monthly up to five pre‐seasonal injections. Safety monitoring followed the Medical Dictionary for Regulatory Activities (MedDRA); efficacy parameters were determined according to the European Academy for Allergy and Clinical Immunology ( EAACI ) guidelines; allergen‐specific antibodies and basophil sensitivity were determined by ELISA and basophil activation testing, respectively. Results A dose‐dependent reduction of the combined symptom medication score ( CSMS ) (40 μg: 17.41%; 80 μg: 24.13%) over placebo was observed which was significant for the 80 μg group and accompanied by the strongest induction of Bet v 1‐specific IgG (median 20‐fold increase) and a blunting of the seasonally boosted IgE response and basophil sensitivity. The vaccine showed an acceptable safety profile despite high administered doses. Conclusion A pre‐seasonal course of 5 monthly injections of GNR ‐127 80 μg improved symptoms of birch pollen allergy accompanied by a robust Bet v 1‐specific IgG response, paving the road for a Phase III efficacy study. Trial Registration ClinicalTrials.gov (Identifier: NCT07155499)