RSV F Protein Mutants for Pre-Fusion Conformation Stability
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Solution Overview
Problem
Current RSV vaccines fail to elicit sufficient levels of protection due to the challenge of maintaining the pre-fusion conformation of the RSV F protein, which is crucial for neutralizing antibodies to bind effectively, as the protein often converts to the less effective post-fusion form under stress conditions.
Innovation Solution
Development of RSV F protein mutants with engineered disulfide bonds, cavity-filling mutations, and electrostatic mutations to stabilize the pre-fusion conformation, enhancing immunogenicity and stability.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If the RSV F protein is used as a vaccine antigen, then neutralizing antibody responses can be elicited, but the protein converts to the post-fusion form under stress conditions, reducing vaccine efficacy
Solution Approach 1:
The patent applies parameter changes by introducing specific amino acid substitutions at defined positions in the F protein sequence. These substitutions alter the physical-chemical parameters of the protein structure, specifically enhancing the stability of the pre-fusion conformation through engineered disulfide bonds and cavity-filling mutations that prevent thermal denaturation and conformational conversion to the post-fusion state
Solution Approach 2:
The patent creates a composite structure by combining the native F protein sequence with engineered stabilizing elements, including disulfide bonds and hydrophobic cavity fillers. This composite approach integrates foreign amino acid residues into the native protein framework to create a hybrid structure that maintains immunogenicity while gaining enhanced thermal and conformational stability
2Stability of the object's composition
If mutations are introduced to stabilize the pre-fusion conformation, then protein stability improves, but the complexity of protein engineering increases
Solution Approach 1:
The patent applies local quality by introducing stabilizing mutations only at specific, strategically chosen positions within the F protein sequence rather than throughout the entire structure. The mutations are localized to regions that provide maximum stabilizing effect with minimal disruption to overall protein function and immunogenicity, such as creating disulfide bonds at defined cysteine positions and filling specific hydrophobic cavities
Data Source
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AI summary
The present disclosure relates to RSV F protein mutants, nucleic acids or vectors encoding a RSV F protein mutant, compositions comprising a RSV F protein mutant or nucleic acid, and uses of the RSV F protein mutants, nucleic acids or vectors, and compositions.