Fusion Polypeptide Vaccine Oligomerization for Cross-Immunity
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Solution Overview
Problem
Current vaccines for viruses like influenza and dengue are ineffective against variant strains and multiple subtypes due to antigen mutations, lacking cross-immunity and cellular immunity induction.
Innovation Solution
A fusion polypeptide is developed, comprising conserved B cell and T cell epitopes from viral antigens, which are oligomerized to enhance immunogenicity and induce both humoral and cellular immune responses across various subtypes.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Device complexity
If monomeric antigen proteins are used in vaccines, then the vaccine can be produced with simpler structure, but the immunogenicity is low and cannot induce strong immune response
Solution Approach 1:
The patent combines multiple antigen molecules into multimeric structures (dimers, trimers, or higher-order multimers) to enhance immunogenicity. This is achieved by fusing antigen coding sequences with oligomerization domain coding sequences, causing the antigen proteins to self-assemble into multimeric forms that strongly induce immune responses while maintaining relatively simple production processes.
Solution Approach 2:
The patent creates composite antigen structures by combining antigen proteins with oligomerization domains in a fusion protein construct. This composite approach allows the antigen to adopt complex multimeric architectures that enhance immune recognition, while the modular design facilitates straightforward genetic engineering and production.
2Reliability
If vaccines use head region of HA antigen which contains major epitopes, then neutralizing antibody response is strong against current strains, but the vaccine has little effect on new mutant strains due to antigen mutations
Solution Approach 1:
The patent divides the HA antigen into functional segments, specifically using the stem region (which is conserved across strains) combined with T cell epitope-containing regions from matrix or nucleocapsid proteins. This segmentation allows the vaccine to target conserved epitopes that elicit cross-reactive antibodies and T cell responses against multiple influenza A subtypes, reducing dependency on strain-specific head region epitopes.
Solution Approach 2:
The patent designs antigens with universal applicability by incorporating conserved stem region sequences that are shared across different influenza A subtypes. The multimeric structure and inclusion of T cell epitopes from conserved matrix/nucleocapsid proteins enhance broad cross-reactivity, making the vaccine effective against multiple strains including mutants, while maintaining strong immunogenicity.
3Reliability
If conventional influenza vaccines are used, then humoral immunity is induced through neutralizing antibodies, but cellular immunity is hardly induced and cross-cell immunity between subtypes is not established
Solution Approach 1:
The patent merges B cell epitope-containing antigens (stem region of HA) with T cell epitope-containing antigens (matrix or nucleocapsid proteins) into a single fusion protein construct. This combination enables simultaneous induction of both humoral immunity (through conserved B cell epitopes) and cellular immunity (through T cell epitopes from matrix/nucleocapsid proteins), establishing cross-subtype protection while maintaining strong immunogenicity through multimeric structure.
Data Source
AI summary
The present invention provides a fusion polypeptide that induces a humoral immune response and a cellular immune response to a virus, containing antigens or fragments thereof of the following (a) and (b), and having an oligomerization activity:(a) an antigen of the virus or a fragment thereof containing a B cell epitope conserved among subtypes of the virus; and(b) an antigen of the virus or a fragment thereof containing a T cell epitope conserved among subtypes of the virus(wherein the antigen(s) or the fragment(s) thereof of (a) and/or (b) have an oligomerization activity, or the fusion polypeptide further contains (c) a polypeptide having an oligomerization activity in addition to the antigens or the fragments thereof (a) and (b)).