Polyprotein Vaccine With Non-Host T-Cell Epitopes to Break Self-Tolerance
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Solution Overview
Problem
Existing vaccines and treatments for conditions involving aberrant cytokine production, such as atopic dermatitis and asthma, face challenges in breaking self-tolerance to self-proteins like IL-31, IL-4, IL-5, IL-13, and IL-33, due to high production costs, complexity, and short-lasting effects, and require frequent administration.
Innovation Solution
A vaccine composition comprising a polyprotein with self-protein segments and non-host T-cell epitopes, combined with immunostimulatory oligonucleotides, induces a potent immune response, producing autoantibodies that neutralize the self-proteins, providing a long-lasting therapeutic effect.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If fusion proteins comprising self and non-self proteins are used to break self-tolerance, then autoantibodies can be generated against self-proteins, but the production cost and complexity increase
Solution Approach 1:
The invention divides the self-protein into multiple segments (at least two self-protein segments) that are incorporated into the polyprotein structure. This segmentation allows the vaccine to present multiple epitopes from the same self-protein, enhancing the immune response while maintaining a manageable composition structure. The segments are arranged in a specific pattern with non-self protein segments interspersed between them.
Solution Approach 2:
The invention merges multiple self-protein segments with non-self protein segments into a single polyprotein structure. This combination allows the vaccine to simultaneously present both self and non-self epitopes, facilitating T-cell help for B-cell activation while maintaining a unified molecular structure that simplifies production compared to separate fusion protein formulations.
2Reliability
If conventional vaccines are used to treat cytokine-related diseases, then treatment can be achieved, but the duration of action is short requiring frequent administration
Solution Approach 1:
The invention designs the polyprotein to induce continuous production of autoantibodies against the target self-protein. By incorporating multiple self-protein segments in a specific arrangement, the vaccine maintains sustained immune activation, ensuring long-lasting therapeutic effect. The autoantibodies generated continue to neutralize the pathogenic cytokines for extended periods, reducing the need for frequent readministration.
3Adaptability or versatility
If multiple different cytokines are targeted in vaccine development, then comprehensive disease treatment is achieved, but the manufacturing precision and complexity increase
Solution Approach 1:
The invention creates a universal polyprotein structure that can be designed to target multiple different cytokines by incorporating segments from various self-proteins (e.g., IL-4, IL-5, IL-13, IL-31, IL-33, TNF-alpha). The same basic polyprotein architecture with interspersed non-self segments can be adapted to different cytokine combinations, allowing a single platform to address multiple disease targets without requiring entirely new vaccine designs for each cytokine.
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 polyprotein-based vaccine effectively breaks self-tolerance, eliciting autoantibodies that persist in the host's circulation for weeks, neutralizing the target self-proteins and reducing disease symptoms with reduced frequency of administration and lower production costs.
Implementation Method 1
induces a potent immune response, producing autoantibodies that neutralize the self-proteins
Implementation Method 2
autoantibodies that persist in the host's circulation for weeks, neutralizing the target self-proteins
Data Source
AI summary
The present invention relates to a vaccine composition for breaking self-tolerance against a self-protein of a host, in particular for breaking self-tolerance against endogenous cytokines, in particular against the endogenous IL-4, IL-5, IL-13, IL-31 and IL-33 proteins in an animal host. The vaccine composition of the invention contains a polyprotein, a DNA encoding for the polyprotein and/or an RNA encoding for the polyprotein and one or more immunostimulatory oligonucleotides. The polyprotein comprises at least two self-protein segments of the host and one or more T-cell epitopes of non-host origin in between and/or adjacent to the at least two self-protein segments.The present invention further concerns the use of the vaccine composition for the prevention and/or treatment of diseases including the prevention and/or treatment of a pruritic condition and/or an allergic condition. In another aspect, the present invention provides a method for detecting the presence of autoantibodies against self-proteins that can be generated with the vaccine composition of the invention.