Viral Trimeric Antigens Stabilized by Disulfide Bond Belts
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Solution Overview
Problem
Current vaccines for enveloped viruses, such as influenza and HIV, face challenges in stabilizing viral trimeric antigens, which affects their resistance to environmental stress and immune response efficacy.
Innovation Solution
Introduction of a tandem disulfide bond belt formed by two-cysteine mini-domains in the viral surface antigenic proteins, specifically in the transmembrane domain, to stabilize the trimeric structure and enhance immune responses.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Stability of the object's composition
If conventional vaccines for enveloped viruses are used, then the viral surface antigens can be presented to the immune system, but the trimeric structure is unstable and susceptible to environmental stress
Solution Approach 1:
The patent introduces a hybrid structure combining viral transmembrane domains with engineered two-cysteine mini-domains. This composite approach creates a stabilized trimeric complex where the cysteine bridges form additional covalent connections between monomers, reinforcing the trimeric structure without altering the antigenic surface properties. The mini-domains act as molecular staples that lock the trimeric configuration against environmental stress.
2Reliability
If the viral surface antigens are stabilized using conventional methods, then structural integrity is improved, but the immune response efficacy remains insufficient
Solution Approach 1:
The stabilization strategy is applied locally at the transmembrane domain region rather than throughout the entire antigen structure. The two-cysteine mini-domains are specifically positioned in the membrane-anchoring portion of the protein, allowing the immunogenic ectodomain to maintain its native conformation and antigenic determinants while the transmembrane region provides structural reinforcement through disulfide bonding.
3Strength
If the trimeric structure is stabilized with additional bonds, then resistance to stress increases, but the complexity of the protein structure increases
Solution Approach 1:
The two-cysteine mini-domains serve as intermediary elements that mediate between the viral transmembrane domain and the trimeric interface. These small, defined peptide sequences (CxxC, CxxxC, or CxxxxC patterns) act as molecular connectors that form disulfide bridges between adjacent monomers, providing structural reinforcement without requiring complex tertiary structures or large domain additions.
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 stabilization of viral trimeric antigens leads to increased resistance to pH and temperature treatments and elicits stronger cross-reactive immune responses, improving vaccine efficacy against enveloped viruses.
Implementation Method 1
the two cysteines in the two-cysteine mini-domain could form a tandem disulfide bond belt, covalently tighting the homotrimer
Data Source
AI summary
The present invention provides a recombinant viral surface antigenic protein with enhanced stability. The present invention also provides a vaccine composition against enveloped viruses.