Consensus Neuraminidase Vaccine Composition for Broad Strain Protection
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Solution Overview
Problem
Current influenza vaccines are ineffective against a wide range of influenza strains due to variability in the hemagglutinin (HA) protein and lack of standardization in neuraminidase (NA) content, leading to significant morbidity and mortality even in vaccinated populations.
Innovation Solution
A cluster-based consensus (CBC) approach is used to generate NA polypeptides by aligning sequences, identifying clusters, determining consensus and variable amino acids, and performing molecular modeling to create recombinant NA polypeptides that elicit a broadly reactive immune response.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If current influenza vaccines are updated annually to accommodate variations in circulating influenza strains, then vaccine effectiveness against predicted strains is improved, but vaccine mismatch resulting from inaccurate predictions leads to significant morbidity and mortality
Solution Approach 1:
The patent applies universality by designing NA-based vaccine compositions that can protect against multiple influenza strains simultaneously. The conserved NA sequences are selected to elicit immune responses that are effective across different influenza types and subtypes, making a single vaccine composition universally protective rather than strain-specific
Solution Approach 2:
The patent changes the parameter of vaccine antigen selection from variable HA sequences to conserved NA sequences. By selecting NA sequences with high degree of conservation across strains and optimizing the NA:HA ratio in the vaccine composition, the vaccine achieves broader protective efficacy without requiring annual updates
2Reliability
If influenza vaccines are based on inducing immune responses to HA, then immune response against circulating strains is improved, but variability in HA results in vaccines being effective only against a small subset of related circulating strains
Solution Approach 1:
The patent extracts the NA component from the traditional HA-based vaccine formulation and makes it the primary antigen. By taking out NA and focusing vaccine design on its conserved sequences, the patent achieves cross-strain protection while maintaining effective immune response induction
Solution Approach 2:
The patent creates a composite vaccine composition containing both NA and HA antigens in optimized ratios. This composite approach combines the cross-strain protection capability of conserved NA sequences with the immunogenicity of HA, achieving both reliability and adaptability
3Adaptability or versatility
If NA is included in influenza vaccine compositions, then broad protective response is improved, but the content and activity of NA is not standardized in current vaccine formulations
Solution Approach 1:
The patent changes the parameter of NA sequence selection by using bioinformatics approaches to identify conserved NA sequences across influenza strains. This systematic selection method ensures that the NA component in the vaccine formulation has standardized and optimized content for eliciting broad protective immune responses
Solution Approach 2:
The patent employs feedback mechanisms through iterative testing and characterization of NA sequences. By assessing the immunogenicity and protective efficacy of different NA sequences and formulations, the patent optimizes and standardizes the NA content in vaccine compositions
Data Source
AI summary
The present disclosure relates to a cluster-based consensus approach for generating recombinant neuraminidase (NA) polypeptides. The disclosure further relates to influenza vaccine compositions comprising the recombinant NA polypeptides.