A mutant of the major apple allergen, Mal d 1, demonstrating hypo‐allergenicity in the target organ by double‐blind placebo‐controlled food challenge

摘要: Summary Background Allergen-specific immunotherapy for food allergy has been hindered by severe side-effects in the past. Well-characterized hypo-allergenic recombinant allergens potentially offer a safe solution. Objective To demonstrate hypo-allergenicity of mutated major allergen from apple, Mal d 1, vitro and vivo. Methods A mutant apple allergen, was obtained site-directed mutagenesis exchanging five amino acid residues. Fourteen patients with combined birch pollen-related were included study. Hypo-allergenicity rMal 1 (rMal 1mut) compared assessed methods, i.e. RAST (inhibition), immunoblotting basophil histamine release (BHR) vivo skin prick test double-blind placebo-controlled challenge (DBPCFC). Results analysis (n=14) revealed that IgE reactivity to 1mut twofold lower than wild-type molecule (95% confidence interval (CI): 1.7–2.4). inhibition (n=6) showed 7.8-fold decrease IgE-binding potency CI: 3.0–12.6). In contrast this moderate potency, biological activity SPT BHR decreased 10–200-fold. confirmed DBPCFC (n=2) both molecules. Conclusion translates into potent activity. This is first study confirms clinically hypo-allergenic. paves way towards safer treatment food-allergic patients.