Peptide Conjugate Vaccines Using Fusion Polypeptides to Overcome Tolerance
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Solution Overview
Problem
Existing protein-based vaccines face challenges in eliciting a strong immune response against both non-self and self-antigens, particularly due to poor immunogenicity and immunological tolerance mechanisms.
Innovation Solution
The use of fusion polypeptides comprising non-mammalian antigens linked with immune stimulating peptides, optimized for specific criteria such as amino acid ratios, isoelectric point, and solubility, to enhance immune responses.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If protein-based vaccines are used to elicit immune response against self-antigens, then the vaccine can target tumor-specific antigens, but the immune response is suppressed due to immunological tolerance mechanisms
Solution Approach 1:
The patent combines self-antigens with immune-stimulating peptide sequences to create fusion polypeptides. This merging allows the vaccine to maintain targeting specificity for self-antigens while simultaneously activating the immune system to overcome tolerance mechanisms and elicit a protective immune response against cancer cells.
Solution Approach 2:
The invention creates composite vaccine structures by fusing immune-stimulating peptide sequences with self-antigen sequences. These composite fusion polypeptides function as a unified immunogen that both presents the self-antigen to T cells and provides co-stimulatory signals to activate the immune response, effectively converting a tolerogenic stimulus into an immunogenic one.
2Reliability
If protein-based vaccines are used against non-self antigens, then the vaccine can target infectious disease antigens, but the immune response is insufficient due to poor immunogenicity
Solution Approach 1:
The patent merges weakly immunogenic non-self antigens with strongly immunogenic peptide sequences. This combination ensures that the antigen-specific T cell response is maintained while the immune-stimulating sequences provide the necessary co-stimulatory signals to amplify the overall immune response to protective levels.
Solution Approach 2:
The invention changes the immunogenicity parameters of the vaccine by incorporating peptide sequences with known high immunogenicity and co-stimulatory activity. This parameter modification transforms a suboptimal immunogen into a highly effective vaccine that elicits robust humoral and cellular immune responses.
3Device complexity
If standard protein-based therapeutics are used, then the treatment can be simple in design, but the immune response is too weak to be clinically effective
Solution Approach 1:
The patent combines simple protein-based antigen sequences with immune-stimulating peptide sequences in a single fusion polypeptide. This approach maintains the simplicity of protein-based therapeutics while adding the necessary immunogenicity elements to achieve clinical efficacy, avoiding the need for complex adjuvant formulations or delivery systems.
Data Source
AI summary
The present invention provides novel fusion polypeptides and compositions comprising the same. The fusion polypeptides are able to trigger and/or enhance an immune response against a peptide sequence of interest comprised therein and therefore are useful for vaccinating or treating a mammalian subject. Kits comprising the fusion polypeptide are also provided.