Mosaic Influenza HA and NA Polypeptides for Broad Strain Coverage
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Solution Overview
Problem
Current influenza vaccines require annual updates based on predicted strains and struggle to induce broad immunity due to the high variability of hemagglutinin antigen across influenza virus strains.
Innovation Solution
Engineering mosaic influenza antigenic polypeptides by combining epitope patterns from multiple HA and NA sequences to create polypeptides that maximize exposure to conserved regions, enhancing strain coverage and inducing a broadly neutralizing immune response.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Adaptability or versatility
If current influenza vaccines are designed to induce strain-specific immunity, then they provide effective protection against predicted strains, but they fail to provide broad immunity across multiple influenza virus strains
Solution Approach 1:
The hemagglutinin antigen is segmented into multiple epitope regions from different influenza strains. The vaccine design isolates and combines specific epitope sequences (e.g., from H1N1, H3N2, and influenza B strains) to create a mosaic antigen that presents diverse epitopes to the immune system, thereby expanding strain coverage while maintaining immunogenicity
Solution Approach 2:
The vaccine employs a composite antigen structure where epitope sequences from multiple different influenza virus strains are combined into a single chimeric hemagglutinin polypeptide. This composite approach integrates conserved and variable regions from different strains (H1, H3, B lineages) to create an antigen that elicits broad cross-strain immune responses
2Adaptability or versatility
If influenza vaccines are updated annually based on predicted strains, then they maintain relevance to circulating viruses, but the effort to design and manufacture vaccines remains difficult and time-consuming
Solution Approach 1:
The mosaic hemagglutinin antigen is designed in advance to include epitopes from multiple potential influenza strains (H1N1, H3N2, influenza B lineages) simultaneously. This preliminary incorporation of diverse epitopes creates a vaccine that is pre-adapted to cover multiple strains, reducing the need for rapid annual redesign and manufacturing reconfiguration
Solution Approach 2:
The vaccine antigen is engineered to serve multiple functions by incorporating epitopes that recognize multiple influenza virus types and lineages. A single vaccine formulation can elicit immune responses against H1, H3, and B strains, providing universal protection that reduces the complexity of annual vaccine updates
3Adaptability or versatility
If the hemagglutinin antigen is highly variable across influenza virus strains, then it enables viral diversity and immune evasion, but it prevents the induction of broad immunity by vaccines
Solution Approach 1:
The mosaic antigen design applies local quality by selectively incorporating specific epitope regions from different influenza strains while maintaining the overall hemagglutinin structure. Conserved epitope regions are emphasized in the mosaic construction to ensure broad recognition, while variable regions are strategically selected to maintain viral-like immunogenicity without compromising structural integrity
Solution Approach 2:
The vaccine uses composite antigen construction where epitope sequences from highly variable influenza strains are combined in a controlled mosaic pattern. This composite approach balances viral diversity (by including variable epitopes) with immunogenic consistency (by incorporating conserved epitopes), enabling broad immune recognition across strains
Data Source
AI summary
The present invention provides, among other things, a novel and improved method for generating “mosaic” influenza antigenic polypeptides including hemagglutinin (HA) and neuraminidase (NA) polypeptides based on unique combination of epitope patterns that maximize exposure to epitopes present across multiple HA or NA sequences and therefore improved influenza strain coverage. In particular, the present invention provides engineered influenza B hemagglutinin (HA) polypeptides that are comprised of novel combinations of protective epitopes and antigenic regions from multiple influenza B viral strains. Such engineered HA polypeptides have improved properties over HA polypeptides developed through conventional approaches that rely on consensus alignments of viral sequences.