Modified S Protein Trimer Antigen for Variant Efficacy
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Solution Overview
Problem
Current coronavirus vaccines face reduced efficacy against emerging variants due to mutations in the RBD and NTD of SARS-CoV-2, leading to diminished neutralization potency of convalescent and vaccine-induced immune sera, necessitating improved antigens for eliciting immune responses against variants of concern.
Innovation Solution
A coronavirus vaccine antigen comprising a modified S protein trimer with reduced alanine cavity size in the coiled-coil region, stabilized by substituting amino acids with more hydrophobic residues, which enhances thermal stability and elicits neutralizing antibody responses.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Stability of the object's composition
If amino acid substitutions with more hydrophobic residues are introduced to stabilize the S protein trimer structure, then thermal stability is improved, but protein structure complexity increases
Solution Approach 1:
The patent applies parameter changes by systematically substituting amino acid residues at specific positions (985, 986, 987, 988, 989, 990) in the S protein trimer with residues having different hydrophobicity values. This changes the physical-chemical parameters of the protein structure, optimizing the balance between thermal stability and structural complexity through controlled modification of hydrophobic interactions in the coiled-coil region.
2Reliability
If the S protein trimer structure is modified to reduce alanine cavity size, then immunogenicity is improved, but manufacturing precision requirements increase
Solution Approach 1:
The patent applies local quality by introducing specific amino acid substitutions at defined positions (985-990) within the coiled-coil region of the S protein trimer. These localized modifications reduce the alanine cavity size and improve immunogenicity without requiring global structural changes, thereby managing manufacturing precision requirements through targeted rather than comprehensive modifications.
Solution Approach 2:
The patent systematically varies amino acid residues at specific positions to optimize the alanine cavity dimensions. By changing the physical parameters (hydrophobicity, side chain volume) at these specific locations, the patent achieves improved immunogenicity while maintaining controllable manufacturing precision through defined substitution patterns.
3Reliability
If amino acid substitutions are made to enhance neutralizing antibody responses against variants, then vaccine efficacy is improved, but protein sequence complexity increases
Solution Approach 1:
The patent applies parameter changes by substituting amino acid residues at positions 985-990 with residues having optimized hydrophobicity values. This systematic parameter optimization enhances the stability and immunogenicity of the S protein trimer, improving vaccine efficacy against variants while managing sequence complexity through targeted substitutions rather than extensive sequence changes.
Solution Approach 2:
The patent applies local quality by focusing amino acid substitutions specifically in the coiled-coil region (positions 985-990) rather than throughout the entire S protein sequence. This localized approach enhances vaccine efficacy through improved trimer stability and immunogenicity while minimizing overall protein sequence complexity by leaving the rest of the sequence unchanged.
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 S protein trimer antigen demonstrates improved stability and immunogenicity, inducing robust neutralizing antibody responses against both wild-type and variant strains, including highly resistant variants like Beta and Omicron, thereby maintaining vaccine efficacy against emerging viral variants.
Implementation Method 1
stabilized by substituting amino acids with more hydrophobic residues, which enhances thermal stability
Implementation Method 2
elicits neutralizing antibody responses
Data Source
AI summary
The field of the specification relates broadly to SARS-CoV-2 vaccine spike protein antigens and methods of using and manufacturing these antigens. The invention also relates to vectors and polynucleotides encoding the SARS-CoV-2 vaccine antigens and vaccines, kits, devices and strips comprising the coronavirus vaccine antigen. The spike protein from SARS-CoV-2 has prolines substituted at positions 986, 987 (2P or S-2P) and additional alanine cavity filling mutations at positions A1016 and A1020.