Consensus HA Protein for Broadly Reactive Influenza Immunity
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Solution Overview
Problem
Current influenza vaccines, particularly those targeting H5N1 viruses, often fail to induce broad protective immune responses and are limited in their ability to prevent infection across various virus isolates, leading to concerns about pandemic potential.
Innovation Solution
Development of an optimized influenza hemagglutinin (HA) protein through alignment and consensus sequence generation for clade 2 H5N1 virus isolates, optimized for expression in mammalian cells, which is used to create virus-like particles (VLPs) to elicit a broadly reactive immune response.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Adaptability or versatility
If traditional influenza vaccines are used, then they can induce humoral immune responses, but they fail to elicit broadly reactive immune responses across different H5N1 virus isolates
Solution Approach 1:
The patent applies parameter changes by modifying the amino acid sequence of the hemagglutinin protein to create a consensus sequence that represents multiple H5N1 virus clades. This sequence optimization changes the antigenic parameters to elicit broadly reactive antibodies that recognize multiple virus isolates, thereby improving adaptability while maintaining protective immunity
Solution Approach 2:
The optimized hemagglutinin protein serves multiple functions by being designed to elicit immune responses against multiple H5N1 virus clades simultaneously. This universal antigen can protect against diverse virus isolates, making a single vaccine formulation effective across different viral variants
2Quantity of substance
If inactivated vaccines are used, then they can efficiently induce humoral immune responses, but they generally only induce poor cellular immune responses
Solution Approach 1:
The patent changes the immunogenic parameters of the vaccine by using an optimized consensus hemagglutinin sequence that enhances both humoral and cellular immune responses. The sequence optimization improves antigen recognition and presentation, thereby increasing cellular immunity while maintaining humoral response levels
3Adaptability or versatility
If consensus sequences are generated for multiple H5N1 clades, then broadly reactive antibodies are elicited, but the vaccine complexity increases
Solution Approach 1:
The patent merges multiple clade-specific antigenic determinants into a single consensus hemagglutinin sequence. This consolidation combines the protective epitopes from multiple virus clades into one unified antigen, thereby achieving broad reactivity while simplifying the vaccine formulation to a single protein sequence
Solution Approach 2:
The optimized hemagglutinin protein serves as a universal antigen that can protect against multiple H5N1 virus clades simultaneously. This single multi-functional antigen replaces the need for multiple clade-specific vaccine formulations, reducing overall vaccine complexity
Data Source
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AI summary
Described herein is the development of a computationally optimized influenza HA protein that elicits broadly reactive immune response to all H5N1 influenza virus isolates. The optimized HA protein was developed through a series of HA protein alignments, and subsequent generation of consensus sequences, for clade 2 H5N1 influenza virus isolates. The final consensus HA amino acid sequence was reverse translated and optimized for expression in mammalian cells. It is disclosed herein that influenza virus-like particles containing the optimized HA protein are an effective vaccine against H5N1 influenza virus infection in animals.