Recombinant Equ c 1 Polypeptides for Horse Allergy Immunotherapy
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Solution Overview
Problem
Current treatments for horse allergy rely on allergens purified from natural sources, leading to batch-to-batch variations and potential anaphylactic side effects, with a need for safe and efficient therapies that are underdeveloped.
Innovation Solution
Development of recombinant hypoallergenic Equ c 1 polypeptides with specific amino acid modifications to reduce IgE-binding epitope and monomer-monomer interface interactions, preventing histamine release from basophils and maintaining native-like structure for immunogenic potential.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If allergens are purified from natural sources for allergy treatment, then the treatment can be provided, but batch-to-batch variations and anaphylactic side effects occur
Solution Approach 1:
The patent creates recombinant copies of the Equ c 1 allergen protein through genetic engineering. The wild-type equine c 1 sequence is used as a template to produce recombinant polypeptides in a controlled system, eliminating batch variations while maintaining immunogenicity. The copying process allows for precise control over protein structure and purity.
Solution Approach 2:
The patent modifies specific amino acid parameters in the Equ c 1 sequence to create hypoallergenic variants. Mutations are introduced at positions corresponding to IgE epitopes and dimerization interfaces, changing the protein's allergenic properties while preserving its ability to induce protective immunity. This parameter modification approach reduces anaphylactic reactions.
2Object-affected harmful factors
If amino acid modifications are made to reduce IgE-binding to create hypoallergens, then side effects are reduced, but the structure must be carefully maintained for immunogenic potential
Solution Approach 1:
The patent applies local quality modification by targeting specific regions of the Equ c 1 protein for mutation while leaving other regions unchanged. IgE-binding epitopes and dimerization interfaces are locally modified through site-directed mutagenesis, while the overall protein fold and B-cell epitope regions are preserved to maintain immunogenicity.
Solution Approach 2:
The patent converts the harmful IgE-binding capability into a benefit by using the known IgE epitope structures to guide rational design of mutations. The same regions that cause allergic reactions are identified and modified to reduce IgE binding, while the modified protein still elicits protective immune responses.
3Stability of the object's composition
If dimeric structures are present in allergens, then natural allergen behavior is maintained, but transient dimers may enhance allergenicity
Solution Approach 1:
The patent introduces asymmetry at the dimerization interface through mutations in one or both monomers. This disrupts the symmetric interaction that stabilizes dimer formation, shifting the equilibrium toward monomeric forms. The asymmetric modifications prevent stable dimer while maintaining individual monomer immunogenicity.
Solution Approach 2:
The patent preemptively modifies the dimerization interface to prevent excessive dimer formation before it can enhance allergenicity. By reducing transient dimer populations in advance, the hypoallergenic variants avoid the enhanced allergenic potential associated with dimeric structures while maintaining sufficient protein stability.
Data Source
AI summary
The present invention relates to specific modified Equ c 1 polypeptides and to the use of such polypeptides as hypoallergens for desensitizing against horse allergy. Particularly, the present invention provides a recombinant hypoallergenic Equ c 1 polypeptide comprising at least two amino acid modifications compared to a corresponding wild type Equ c 1 allergen, wherein the recombinant hypoallergenic polypeptide activates release of histamine from basophils to a degree less than the wild type allergen.