Recombinant Hemagglutinin Antigen Rosette Formation
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Solution Overview
Problem
Current methods for producing influenza vaccines, such as those using egg-based systems, face challenges including limited strain growth, antigenic drift, egg allergies, and supply disruptions, while recombinant hemagglutinin (rHA) vaccines struggle with maintaining immunogenicity and correct quaternary structure.
Innovation Solution
A recombinant influenza virus hemagglutinin (rHA) antigen is developed, comprising the extracellular domain, a hydrophobic transmembrane domain, and a heterologous trimerization domain, specifically incorporating a foldon and histidine tag for proper folding and rosette structure formation, avoiding large aggregates and maintaining immunogenicity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If egg-based methods are used for vaccine production, then large-scale production is achieved, but antigenic drift and suboptimal protection occur
Solution Approach 1:
The patent extracts only the essential antigenic components (HA and NA proteins) from the virus and produces them recombinantly in cell culture, eliminating the need for live virus propagation in eggs. This extraction of the core immunogenic elements allows production without the antigenic drift problems inherent in egg-based systems.
Solution Approach 2:
The patent creates recombinant copies of the HA and NA proteins using synthetic or cloned genes expressed in mammalian cells. These recombinant proteins are functional copies that maintain immunogenicity while being produced under controlled conditions without requiring egg adaptation, thus preventing antigenic drift.
2Object-affected harmful factors
If recombinant hemagglutinin (rHA) is produced in culture cells, then egg allergy safety is improved, but immunogenicity and quaternary structure maintenance deteriorate
Solution Approach 1:
The patent changes the production parameters by using mammalian cell culture systems (such as HEK293 or CHO cells) that properly fold and glycosylate the HA and NA proteins, maintaining their native quaternary structures and immunogenicity. This parameter change from bacterial to mammalian expression systems resolves the immunogenicity issue while maintaining the egg-free advantage.
3Manufacturing precision
If recombinant hemagglutinin (rHA) is produced in culture cells, then production control is improved, but correct rosette structure formation deteriorates
Solution Approach 1:
The patent uses mammalian cells as intermediary hosts that provide the necessary cellular machinery for proper protein folding, disulfide bond formation, and oligomerization. These cells act as mediators that enable the recombinant HA proteins to self-assemble into correct rosette structures while maintaining production control in a defined cell culture system.
Data Source
Figure 1A~1B
Figure 2
Figure 3A~3B
AI summary
The present invention relates to novel influenza antigens, novel immunogenic or vaccine compositions, as well as to uses of and to methods for producing said antigens and compositions. In particular, the invention relates to recombinant forms of hemagglutinin (HA) and their use in vaccine compositions for the prevention of influenza virus infections.