Modified Viral Nucleocapsid Protein Compositions for N-N Dimerization
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Solution Overview
Problem
Existing viral immunization preparations do not effectively enhance antigenicity and dimerization of viral nucleocapsid (N) proteins, particularly in the context of coronavirus variants, which can lead to reduced immune response and viral escape.
Innovation Solution
Incorporating modified viral N proteins with specific amino acid substitutions, such as glycine→cysteine (G→C) or arginine→cystine (R→C) in the linker region, to increase the formation of N-N dimers and enhance antigenicity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If wild-type viral N protein is used in immunization preparation, then the preparation is simple to manufacture, but the antigenicity is insufficient and dimerization level is low
Solution Approach 1:
The patent applies parameter changes by introducing specific amino acid substitutions (G215C, G243C, R185C) in the linker region of the viral N protein to alter its dimerization properties. These point mutations change the chemical parameters of the protein, enabling formation of disulfide bonds that stabilize N-N dimers and increase antigenicity in the immunization preparation.
2Reliability
If amino acid substitutions are introduced in the linker region to increase dimerization, then antigenicity increases, but the protein sequence becomes more complex
Solution Approach 1:
The patent applies local quality by making targeted amino acid substitutions specifically in the linker region (residues 185-263) of the N protein, rather than altering the entire protein sequence. The mutations at positions G215, G243, and R185 are strategically placed to promote local dimerization through disulfide bond formation, thereby enhancing antigenicity while minimizing overall sequence complexity.
3Productivity
If wild-type N protein is used, then manufacturing is straightforward, but immune response is reduced and viral escape is more likely
Solution Approach 1:
The patent converts the previously harmful effect of low dimerization and insufficient antigenicity into a beneficial outcome by introducing specific mutations that promote N-N dimer formation. The mutations create disulfide bond-forming cysteine residues that stabilize dimers, thereby enhancing immune response and reducing viral escape, transforming a weakness into a strength for vaccine efficacy.
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 N proteins increase the level of N-N dimers, thereby enhancing the antigenicity and immune response to viral immunization preparations, potentially inhibiting viral infection and reducing severity.
Implementation Method 1
the modified viral N protein includes an amino acid substitution (also referred to herein as a 'point mutation') in a linker region of a viral N protein... increases a level of N-N dimers
Data Source
AI summary
The invention, in some aspects, relates to compositions comprising modified viral nucleocapsid (N) proteins and their encoding polynucleotides and methods of using such compositions and preparations to increase viral N protein dimerization and/or increase antigenicity of viral immunization preparations.