Ara h 1 Epitopic Peptides Peanut Allergy Tolerance
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Solution Overview
Problem
Current immunotherapy approaches for peanut allergy have limited success due to high rates of anaphylaxis and lack of long-term tolerance, with existing methods failing to effectively target T cell responses and cross-linking of IgE, leading to significant morbidity and safety concerns.
Innovation Solution
Identification and utilization of HLA-degenerate Ara h 1 T cell core epitopic regions that are immunodominant and capable of modifying T cell function without binding to Ara h 1-specific IgE, allowing for the development of diagnostic and therapeutic compositions that induce tolerance and reduce hypersensitivity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If rush immunotherapy protocol is used to induce peanut tolerance, then tolerance can be induced, but tolerance is lost in approximately half of the subjects during maintenance dosing and frequent episodes of anaphylaxis occur
Solution Approach 1:
The patent segments the peanut allergen Ara h 1 into multiple distinct T cell epitopic regions (e.g., SEQ ID NO:1-10). By targeting specific epitopic regions rather than the whole allergen, the therapy divides the immunological challenge into manageable components that can be addressed individually, reducing the risk of severe systemic reactions while maintaining efficacy.
Solution Approach 2:
The patent uses peptide analogs as intermediary molecules that mimic the immunogenic epitopes of Ara h 1 but with modified properties. These peptide intermediaries can induce T cell tolerance without triggering the same level of IgE-mediated anaphylaxis as the native allergen, serving as a safer bridge to induce tolerance.
2Reliability
If oral immunotherapy with whole peanut flour is used, then desensitization is feasible, but major safety concerns arise from observed adverse reactions
Solution Approach 1:
The patent extracts and isolates specific T cell epitopic regions from the complex whole peanut allergen Ara h 1. By taking out only the essential immunogenic peptides (e.g., SEQ ID NO:1-10) and using them as therapeutic agents, the therapy removes the harmful components present in whole peanut flour while retaining the ability to induce desensitization.
Solution Approach 2:
The patent modifies the physical and chemical parameters of the allergen by using synthesized peptide analogs instead of whole peanut flour. These peptide variants have altered properties - they maintain T cell epitope recognition but have reduced capacity to trigger severe IgE-mediated reactions, changing the safety profile while preserving therapeutic effect.
3Ease of manufacture
If existing immunotherapy methods are used, then treatment can be provided, but they fail to effectively target T cell responses and cross-linking of IgE
Solution Approach 1:
The patent identifies HLA-degenerate epitopic regions that can be presented by multiple HLA class II molecules (e.g., HLA-DQ, HLA-DR). This universality allows the same peptide therapy to effectively target T cells across different individuals with varying HLA types, making the treatment broadly applicable and effective without requiring personalized HLA matching.
Data Source
AI summary
The present invention relates generally to molecules such as peptides, polypeptides and proteins which interact immunologically with T lymphocytes in subjects having peanut allergy, or allergy to other tree nuts, and genetic sequences encoding same. These molecules are preferably immunointeractive with T cells in subjects having an allergy to the Ara H 1 allergen. The molecules of the present invention are useful in the development of diagnostic, therapeutic and prophylactic agents for conditions characterised by an aberrant, inappropriate or otherwise unwanted immune response to Ara h 1 or derivative or homologue thereof.