Modified VZV gE Protein Disulfide Bridges for Thermostability
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Solution Overview
Problem
Existing recombinant subunit vaccines, such as those containing VZV gE, face challenges with protein instability, leading to reduced shelf life and reliance on cold storage, and may not elicit optimal immune responses.
Innovation Solution
Modified VZV gE proteins with non-native disulfide bridges and specific amino acid sequences are developed to enhance thermostability and immunogenicity, reducing the amount of antigen or adjuvant required for effective immune response.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of manufacture
If non-modified VZV gE protein is used in vaccine composition, then the vaccine can be developed with simpler protein structure, but the protein exhibits reduced stability and shorter shelf life requiring cold storage
Solution Approach 1:
The patent introduces non-native disulfide bridges at specific cysteine pairs (e.g., Cys-365 and Cys-477, Cys-427 and Cys-434) to modify the protein's structural parameters. This chemical modification increases thermostability and extends shelf life without fundamentally changing the overall protein architecture or manufacturing complexity
Solution Approach 2:
The modified VZV gE protein combines native amino acid sequences with introduced cysteine residues forming non-native disulfide bridges, creating a composite structural system that integrates both simple native folding and stabilized cross-linked regions for enhanced stability
2Duration of action of stationary object
If non-native disulfide bridges are introduced to improve thermostability, then shelf life is extended, but the protein structure becomes more complex
Solution Approach 1:
The patent makes targeted parameter changes by introducing disulfide bridges at specific, limited cysteine pairs rather than throughout the entire protein. This localized modification approach extends shelf life while minimizing overall structural complexity increases
Solution Approach 2:
The non-native disulfide bridges are introduced at specific local regions (specific cysteine pairs) rather than uniformly throughout the protein. This local modification strategy provides stability enhancement at critical sites without complicating the entire protein structure
3Device complexity
If standard amounts of antigen are used with non-modified VZV gE, then the formulation is simpler, but optimal immune response is not achieved
Solution Approach 1:
The modified protein's enhanced stability and immunogenicity properties change the effective parameters of antigen presentation and immune recognition, leading to improved immune response efficacy while maintaining standard formulation approaches
Solution Approach 2:
The patent extracts and enhances the immunogenicity property of the VZV gE protein through disulfide bridge modification, separating the stability enhancement from the need for complex adjuvant formulations or higher antigen doses
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The modified VZV gE proteins exhibit increased thermostability and improved immune responses, extending shelf life and enhancing the efficacy of immunogenic compositions.
Implementation Method 1
a modified VZV gE protein comprising at least one cysteine pair capable of forming a non-native disulfide bridge
Data Source
AI summary
Described are modified Varicella Zoster Virus glycoprotein E (VZV gE) proteins having improved stability and/or immunogenicity compared to a non-modified VZV gE. Also described are associated nucleic acids, immunogenic compositions, and methods of using such modified VZV gE proteins in the treatment or prevention of shingles.