Hypoallergenic Par j 1 Variants for Allergy Immunotherapy
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Solution Overview
Problem
Current specific immunotherapy (SIT) for allergic diseases caused by pollen, such as Parietaria, faces challenges due to the risk of serious side effects from traditional vaccines, limiting its use effectively in treating allergic conditions like asthma and rhinitis, and there is a need for safer, hypoallergenic alternatives.
Innovation Solution
Development of hypoallergenic protein variants of the Parietaria judaica major allergen Par j 1 with modified amino acid sequences, which reduce IgE reactivity by 50% to 82%, allowing for the creation of safer pharmaceutical compositions for immunotherapy, including vaccines for allergic diseases like asthma and rhinitis.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If traditional vaccines are used for specific immunotherapy, then therapeutic effect is achieved, but risk of serious side effects increases
Solution Approach 1:
The patent applies parameter changes by modifying the amino acid sequence of the Par j 1 allergen to create variants with reduced IgE reactivity. Specific substitutions (e.g., Lys42→Gln, Lys102→Gln) and deletions alter the protein's epitopic structure, reducing its ability to bind IgE antibodies while preserving its ability to induce immunological tolerance, thereby maintaining therapeutic effect while reducing side effects
Solution Approach 2:
The patent converts the harmful allergenicity of Par j 1 into a benefit by creating hypoallergenic variants. The wild-type allergen's strong IgE-binding capacity is modified through amino acid substitutions and deletions to reduce reactivity by 50-80%, transforming a harmful substance into a safe therapeutic agent that can still induce immunological tolerance without causing severe allergic reactions
2Object-affected harmful factors
If allergen sequence is modified to reduce IgE reactivity, then safety is improved, but allergenic efficacy may be reduced
Solution Approach 1:
The patent applies local quality by making specific localized modifications to the Par j 1 sequence rather than global changes. targeted amino acid substitutions at positions 42 and 102, and selective deletions of specific epitopic regions, preserve the overall protein structure and immunotherapeutic capacity while reducing IgE reactivity in specific critical regions
Solution Approach 2:
The patent applies partial action by implementing moderate amino acid modifications rather than complete sequence alteration. The variants maintain sufficient homology to the wild-type allergen to preserve immunotherapeutic efficacy while achieving partial reduction in IgE reactivity (50-80%), balancing safety and effectiveness
Data Source
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AI summary
The invention provides hypoallergenic Par j 1 sequence-variants and their uses in the treatment of allergic diseases caused by pollen of plants of the species Parietaria.