Influenza Immunogenic Composition With Conserved HA Head-Domain Substitutions
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Solution Overview
Problem
Current influenza vaccines face challenges due to rapid antigenic evolution of the virus, requiring frequent updates and often providing only 10-60% efficacy, with existing 'universal' vaccines targeting weakly immunogenic epitopes and lacking robust protection against various strains.
Innovation Solution
Development of an immunogenic composition comprising polypeptides with specific amino acid substitutions in the haemagglutinin head domain, designed to induce strong immune responses against influenza A strains, particularly H1N1, by targeting epitopes of limited variability.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional influenza vaccines are used, then they provide some protection, but they require frequent updates and only achieve 10-60% efficacy due to rapid antigenic evolution
Solution Approach 1:
The patent applies universality by designing a vaccine that targets conserved epitopes shared across multiple influenza A subtypes (H1N1, H3N2, H5N1, etc.). The polypeptides are engineered to contain epitopes from different influenza strains that share common antigenic determinants, enabling a single vaccine formulation to provide broad protection against diverse influenza variants without requiring frequent updates.
Solution Approach 2:
The patent applies local quality by focusing on specific conserved regions within the influenza virus structure, particularly the haemagglutinin head domain and stem region. Instead of targeting highly variable surface epitopes, the invention identifies and targets locally conserved epitopes that remain relatively unchanged across different influenza strains, thereby achieving reliable and durable immunity.
2Adaptability or versatility
If universal vaccines target invariant epitopes, then they aim for broad protection, but the epitopes have low natural immunogenicity
Solution Approach 1:
The patent applies merging by combining multiple conserved epitopes from different influenza A subtypes into single polypeptide constructs. By fusing epitopes from H1N1, H3N2, H5N1 and other strains into chimeric polypeptides, the vaccine enhances the immunogenicity of individual conserved epitopes through synergistic effects while maintaining broad protective coverage.
Solution Approach 2:
The patent applies composite materials by creating composite polypeptide structures that incorporate multiple conserved epitopic regions from different influenza viruses. These composite polypeptides function as multivalent antigens, presenting multiple conserved epitopes simultaneously to the immune system, thereby overcoming the low immunogenicity of individual invariant epitopes.
3Reliability
If vaccines target highly variable epitopes, then they induce strong immune responses, but the virus evolves rapidly requiring continuous vaccine updates
Solution Approach 1:
The patent applies inversion by reversing the conventional vaccine strategy. Instead of targeting the highly variable epitopes that dominate traditional influenza vaccines, the invention targets the opposite approach—conserved, invariant epitopes that are normally overlooked. This inverted strategy targets the structurally constrained regions of the virus that cannot tolerate mutation, thereby achieving both strong immune responses and long-term vaccine effectiveness.
Data Source
AI summary
The present invention relates to an immunogenic composition comprising two or more polypeptides. The invention also provides nucleic acid molecules and vectors encoding the polypeptides, and methods of using the compositions, nucleic acid molecules and vectors for the prevention or treatment of influenza.