Hypoallergenic Mal d 1 Variants for Allergy Immunotherapy
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Solution Overview
Problem
Current immunotherapy approaches for treating allergies to pollen and food, particularly those caused by cross-reacting allergens like Bet v 1 and Mal d 1, are ineffective and carry risks of severe side effects, as they do not significantly reduce symptoms of food allergies and can induce adverse reactions.
Innovation Solution
Development of hypoallergenic variants of the Mal d 1 protein through site-directed mutagenesis, specifically substituting amino acid residues to reduce IgE reactivity while maintaining the ability to induce protective IgG antibodies, and the creation of hybrid proteins combining hypoallergenic variants of Bet v 1 and Mal d 1 to enhance immunological tolerance.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If standard immunotherapy with birch pollen extract is used to treat apple allergy, then pollen allergy symptoms may improve, but food allergy symptoms remain severe and cross-reactivity is not effectively reduced
Solution Approach 1:
The patent applies parameter changes by modifying the amino acid sequence of the Mal d 1 allergen through site-directed mutagenesis. Specific amino acid residues (Asp25, Asn78) are substituted to alter the molecular structure and reduce IgE reactivity while preserving immunogenicity. This creates hypoallergenic variants that maintain therapeutic effectiveness for pollen allergy while reducing cross-reactivity to food allergens.
Solution Approach 2:
The invention applies local quality by making targeted modifications at specific locations (amino acid positions 25 and 78) of the Mal d 1 protein structure. These localized changes affect only the regions responsible for IgE binding while preserving other functional domains, thereby reducing food allergy cross-reactivity without compromising pollen allergy treatment effectiveness.
2Object-affected harmful factors
If site-directed mutagenesis is used to create hypoallergenic variants, then IgE reactivity is reduced, but the ability to induce protective IgG antibodies must be maintained
Solution Approach 1:
The patent modifies physical-chemical parameters of the allergen by substituting specific amino acid residues (Asp25 with neutral/polar/basic amino acids, Asn78 with neutral/acidic/basic amino acids). These parameter changes reduce IgE binding affinity while the patent demonstrates that the modified proteins retain sufficient immunogenicity to induce protective IgG antibodies, thus resolving the contradiction between reducing harmful IgE reactivity and maintaining beneficial immunogenicity.
3Reliability
If conventional immunotherapy is administered, then some pollen allergy symptoms improve, but there is a high risk of inducing serious side effects including anaphylactic shock
Solution Approach 1:
The patent converts the harmful allergenic properties of Mal d 1 into beneficial hypoallergenic characteristics through controlled mutagenesis. By substituting specific amino acid residues, the invention creates variants that retain immunogenicity for inducing protective immunity against pollen allergy while dramatically reducing IgE reactivity and the risk of anaphylactic shock, thus transforming a harmful substance into a safe therapeutic agent.
Solution Approach 2:
The hypoallergenic variants of Mal d 1 serve as intermediaries between the original allergen and the patient's immune system. These modified proteins mediate the immunotherapy process by inducing protective IgG antibodies without triggering severe IgE-mediated adverse reactions, thus acting as a safe intermediary that provides therapeutic benefit while minimizing harm.
Data Source
AI summary
Disclosed are hypoallergenic variants of Mal d 1, the major allergen from Malus domestica, and the uses thereof in the treatment of allergic diseases.