Modified Allergoids via Dual Chemical Modification
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Solution Overview
Problem
Current allergenic vaccines for immunotherapy in allergic diseases pose risks of severe side effects due to residual allergenic activity, limiting their use and efficacy, especially in food allergies where reactions can be life-threatening.
Innovation Solution
The development of modified allergoids with reduced allergenic activity through a dual chemical modification process using potassium cyanate followed by a dialdehyde or diketone, such as phenylglyoxal, to target lysine and arginine residues, thereby minimizing adverse reactions while maintaining immunogenicity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If standardized extracts containing native allergens are used for immunotherapy, then immunogenicity and ability to induce IgG blocking antibodies are improved, but the risk of severe side effects and anaphylactic reactions increases
Solution Approach 1:
The patent applies chemical modification to change the physical and chemical parameters of allergen molecules, specifically targeting amino groups through carbamylation and other modifications. This alters the allergenic epitopes while preserving immunogenic determinants, thereby reducing side effects while maintaining therapeutic efficacy
Solution Approach 2:
The invention creates composite modified allergen structures by introducing chemical groups (such as carbamyl groups) onto the allergen molecules. These composite structures combine the immunogenic properties of native allergens with reduced allergenicity, achieving both safety and effectiveness
2Object-affected harmful factors
If chemical modification is applied to reduce allergenic activity, then the risk of severe reactions is reduced, but the immunogenic potential may be compromised
Solution Approach 1:
The patent employs selective chemical modification that targets specific local regions of the allergen molecules, particularly amino groups in specific epitopes. This localized modification reduces allergenicity at targeted sites while preserving other regions necessary for immunogenicity and IgG antibody induction
Solution Approach 2:
The modification process applies partial chemical alteration rather than complete denaturation. By controlling the degree and type of modification, the patent achieves sufficient reduction in allergenic activity while maintaining enough structural integrity to preserve immunogenic potential
3Object-affected harmful factors
If multiple sequential chemical modifications are performed, then allergenic activity is significantly reduced (227-fold), but the complexity of the preparation process increases
Solution Approach 1:
The patent divides the chemical modification process into distinct sequential steps, each targeting specific functional groups or epitopes. This segmented approach allows systematic reduction of allergenicity through multiple targeted modifications while enabling control and optimization of each individual step
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The dual modification significantly reduces allergenic activity by 227-folds, as shown in the DP extract example, while preserving immunogenic potential, allowing for effective immunological tolerance induction with reduced risk of severe reactions.
Implementation Method 1
The modified allergens having a reduced allergenicity compared to the corresponding native allergenic material and characterized in that all or a part of the primary amine groups of the lysine and arginine residues of the allergenic molecules are functionalized
Implementation Method 2
the use of a dialdehyde or diketone, such as phenylglyoxal or other similar reagents (glyoxal, 2,3-butanedione, 1,2-cyclohexanedione, para-hydroxyphenylglyoxal, etc.)
Data Source
AI summary
A method of making and a modified allergen having reduced allergenicity and preserved immunogenicity compared to corresponding native allergenic material. The preserved immunogenicity is elicited by a IgG-mediated antibody response, all or part of the primary amine groups of the lysine residues of the native allergenic material are functionalized with carbamoyl or thiocarbamoyl moieties, and all or part of the primary amine groups of the arginine residues of the carbamoyl- or thiocarbamoyl functionalized allergenic material are further functionalized with dialdehyde or diketal moieties. The raw allergenic material is selected from the group consisting of DP mites extract, Der p1, ovalbumin and Lipid Transfer Protein (LTP), the average percentage of modified primary amine groups of the lysine ranges between 75% and 100%; and the average percentage of the substituted arginine residues ranges between 25% and 10%.