Modified RSV F Protein Segmentation for Vaccine Immunogenicity
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Solution Overview
Problem
Current approaches to addressing RSV infection, particularly in young children and immunocompromised individuals, are inadequate due to incomplete resistance and the virus's ability to reinfect, with existing vaccines relying on passive immunization and lacking effective preventive measures.
Innovation Solution
Development of recombinant RSV F proteins with modified or mutated amino acid sequences that enhance expression, reduce cellular toxicity, and improve immunogenicity, used in vaccines and immunogenic compositions to elicit an immune response and prevent RSV infection.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If wild-type RSV F protein is used in vaccines, then the vaccine can induce immune response, but the F protein exhibits cellular toxicity and limited expression levels
Solution Approach 1:
The F protein is divided into two separate polypeptide chains: F1 (residues 1-437) and F2 (residues 438-574). The F1 chain contains the immunogenic domain while the F2 chain contains the transmembrane and cytoplasmic domains. This segmentation removes the toxic effects of the full-length F protein while preserving the immunogenicity of the F1 chain, which can be expressed and purified separately for vaccine use.
2Productivity
If wild-type RSV F protein is expressed in host cells, then the protein can be produced, but expression levels are limited and cellular toxicity occurs
Solution Approach 1:
The toxic transmembrane and cytoplasmic domains (F2 chain) are extracted from the expression system, leaving only the soluble F1 chain to be expressed in host cells. This extraction eliminates the cellular toxicity associated with full-length F protein while allowing high-level expression of the immunogenic F1 fragment in safe, controlled systems.
3Stability of the object's composition
If full-length F protein is used, then the protein maintains native structure, but it forms micelles and exhibits pre-fusion and post-fusion conformations that complicate vaccine design
Solution Approach 1:
The F1 chain is extracted from the full-length F protein, removing the transmembrane and cytoplasmic domains that drive micelle formation and conformational complexity. The isolated F1 chain adopts a stable, simplified structure that is easier to characterize and more suitable for vaccine development, while retaining the critical immunogenic epitopes.
Data Source
AI summary
The present invention is generally related to modified or mutated respiratory syncytial virus fusion (F) proteins and methods for making and using them, including immunogenic compositions such as vaccines for the treatment and/or prevention of RSV infection.