Chimeric Viral Vector Expressing RSV G Protein
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Developing effective vaccines against Respiratory Syncytial Virus (RSV) and Human Parainfluenza Virus 3 (HPIV3) is challenging due to the immaturity of the immune system in infants, immune suppression by maternal antibodies, inefficient immune protection at the respiratory tract, and vaccine-induced enhanced disease in virus-naïve recipients.
Innovation Solution
Recombinant chimeric bovine/human parainfluenza virus 3 (rB/HPIV3) vectors expressing RSV G protein are developed, which are infectious, attenuated, and self-replicating, inducing an immune response to both RSV and HPIV3, with variants of the RSV G protein incorporating different transmembrane and cytoplasmic tail domains to enhance immunogenicity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If inactivated or subunit RSV and HPIV3 vaccines are used, then vaccine safety is improved, but immune protection efficiency deteriorates due to vaccine-induced enhanced disease
Solution Approach 1:
The patent uses a live-attenuated rB/HPIV3 vector as an intermediary carrier to deliver RSV antigens (F and G proteins). This vector-based approach mediates the delivery of immunogenic components without using traditional inactivated or subunit vaccine methods, thereby avoiding vaccine-induced enhanced disease while maintaining immune protection efficiency
Solution Approach 2:
The invention creates a composite vaccine system by combining the rB/HPIV3 viral vector with RSV antigen genes (F and G). This composite approach integrates the advantages of live-vector delivery systems with specific RSV immunogenic components, achieving both safety and efficacy
2Ease of manufacture
If traditional RSV vaccine approaches are used, then vaccine development simplicity is improved, but immunogenicity deteriorates due to immune suppression by maternal antibodies in infants
Solution Approach 1:
The rB/HPIV3 vector serves as an intermediary delivery system that overcomes maternal antibody interference. The vector-based delivery mechanism protects the RSV antigens from neutralization by maternal antibodies, enabling effective immunization in infants despite the presence of passive immunity
Solution Approach 2:
The invention modifies the delivery parameters by using a live-attenuated viral vector instead of traditional inactivated or subunit formulations. This parameter change in delivery mechanism enables the vaccine to function effectively in the presence of maternal antibodies, which suppress traditional vaccine approaches
3Device complexity
If a single RSV antigen is used in the rB/HPIV3 vector, then vaccine complexity is reduced, but immune response completeness deteriorates
Solution Approach 1:
The patent merges multiple RSV antigens (F and G proteins) into a single rB/HPIV3 vector platform. This combining approach maintains relative simplicity in vaccine formulation while achieving comprehensive immune response coverage through the co-expression of multiple viral proteins from different RSV groups
Solution Approach 2:
The rB/HPIV3 vector is designed with multi-functionality to express both RSV F and G antigens simultaneously. This universal platform can accommodate multiple antigen types, providing broad immune protection against different RSV strains and groups without requiring separate vaccine formulations
Data Source
AI summary
Recombinant chimeric bovine/human parainfluenza virus 3 (rB/HPIV3) vectors expressing Respiratory Syncytial Virus (RSV) G protein or a recombinant RSV G protein, as well as methods of their use and manufacture, are provided. The rB/HPIV3 vector comprises a genome comprising a heterologous gene encoding the RSV G protein or the recombinant RSV G protein. Nucleic acid molecules comprising the sequence of the genome or antigenome of the disclosed rB/HPIV3 vectors are also provided. The disclosed rB/HPIV3 vectors can be used, for example, to induce an immune response to RSV and HPIV3 in a subject.