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).