Polyprotein Vaccine Composition for Breaking Self-Tolerance
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Solution Overview
Problem
Existing vaccines and treatments for conditions like atopic dermatitis and asthma, which target self-proteins such as cytokines, face challenges in breaking self-tolerance, are costly, require frequent administration, and involve complex production methods with non-natural components.
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 a self-antigen is covalently coupled to a foreign protein to break self-tolerance, then T-cells specific for the non-self-protein are recruited and activated, but the production cost and complexity increase due to fusion protein requirements
Solution Approach 1:
The invention divides the self-protein into multiple segments (at least two self-protein segments) that are arranged in a specific sequence within the polyprotein. This segmentation allows the vaccine to present multiple epitopes from the same self-protein, enhancing the immune response without requiring complex fusion protein constructions. The self-protein segments are separated by linkers or adjacent to T-cell epitopes, creating a modular structure that simplifies production while maintaining effectiveness.
Solution Approach 2:
The invention creates a composite polyprotein structure combining self-protein segments with foreign T-cell epitopes in a single molecular entity. This composite approach integrates the benefits of self-antigen presentation with foreign immune activation, eliminating the need for separate fusion protein constructions and reducing production complexity while maintaining strong self-tolerance breaking capability.
2Reliability
If monovalent vaccines targeting single self-proteins are used, then the immune response is focused, but the treatment requires frequent administration and is costly
Solution Approach 1:
The invention designs a universal polyprotein vaccine platform that can target multiple self-proteins simultaneously by incorporating segments from different self-proteins (e.g., IL-4, IL-5, IL-13, IL-31, IL-33, TNF-alpha) into a single vaccine construct. This multi-functional approach provides focused immune response against each target while extending treatment duration through sustained production of autoantibodies against multiple cytokines, reducing the frequency of administration.
3Reliability
If existing vaccine approaches are used for atopic dermatitis and asthma, then self-tolerance can be broken, but the production methods involve non-natural components and are costly
Solution Approach 1:
The invention employs synthetic peptides as T-cell epitopes that can be easily produced and incorporated into the polyprotein. These synthetic epitopes replace complex natural protein components, simplifying the manufacturing process and reducing costs. The epitopes are designed to be stable and effective, providing a cost-effective solution for vaccine production without requiring complex purification steps or expensive reagents.
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 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.