Replication-Deficient SeV Vector Expressing Chimeric RSV F Protein
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Solution Overview
Problem
Current RSV vaccines face challenges in safety and efficacy due to genetic instability and residual virulence of live attenuated vaccines, and the limited immune response of replication-deficient viral vectors.
Innovation Solution
A genome replication-deficient Sendai virus (SeV) vector expressing a chimeric RSV/SeV F protein is developed, which is safe and efficiently produced, capable of eliciting strong humoral and cellular immune responses by modifying the phosphoprotein gene to encode a mutant P protein lacking amino acids 2-77 and incorporating a chimeric F protein with an RSV ectodomain and SeV transmembrane domain.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If live attenuated vaccines are used, then good and long-lasting prophylactic humoral and cellular immune responses are generated, but safety concerns arise due to genetic instability and residual virulence
Solution Approach 1:
The patent extracts the harmful replication capability from the viral vector by modifying the phosphoprotein gene to encode a mutant P protein lacking amino acids 2-77, which are essential for viral RNA synthesis. This removes the ability of the vaccine vector to replicate and cause disease while preserving its ability to express immunogenic proteins and stimulate immune responses
Solution Approach 2:
The patent changes the molecular parameters of the phosphoprotein by deleting specific amino acid sequences (amino acids 2-77), fundamentally altering the protein's function from supporting viral replication to supporting only protein expression. This parameter change transforms the vector from potentially harmful live attenuated vaccine to safe replication-deficient vaccine
2Object-affected harmful factors
If replication-deficient viral vectors are used, then safety is improved by preventing genetic instability and residual virulence, but immune response effectiveness is reduced
Solution Approach 1:
The patent makes the replication-deficient SeV vector universally applicable as a vaccine platform by engineering it to express multiple immunogenic proteins including chimeric RSV/SeV F protein, RSV G protein, and other RSV antigens. This multi-functionality compensates for the lack of replication by providing diverse antigenic stimulation to elicit strong immune responses
Solution Approach 2:
The patent creates a composite viral vector system by combining the SeV structural framework with heterologous RSV immunogenic proteins. The chimeric F protein combines RSV ectodomain with SeV transmembrane domain, creating a hybrid protein that leverages properties of both viruses to achieve strong immunogenicity while maintaining safety
Data Source
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AI summary
The present invention relates to a semi-live respiratory syncytial virus (RSV) vaccine, which comprises a genome replication-deficient Sendai virus (SeV) vector expressing a chimeric RSV/SeV F protein. Furthermore, the present invention relates to a method for the production of the genome replication-deficient SeV vector of the present invention, and the use thereof in the treatment of RSV infections and RSV infection-related diseases.