Recombinant HSV-2 Vaccine Vector with Deleted gD Gene
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current vaccines for pathogens like influenza and HIV have limitations and failings, necessitating the development of a novel vaccine strategy that can effectively target various antigenic targets.
Innovation Solution
The development of HSV-2-based vaccines involves creating a recombinant herpes simplex virus-2 (HSV-2) with a deleted glycoprotein D gene, combined with a nucleic acid encoding a fluorescent protein and a heterologous antigen, to produce a vaccine vector that can elicit an immune response against heterologous antigens such as influenza and HIV.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional vaccines are used for influenza and HIV, then they have been developed for these pathogens, but they have failings and limitations in effectiveness
Solution Approach 1:
The HSV-2 vaccine vector is designed to express multiple different heterologous antigens (influenza, HIV, and other pathogens) by replacing the glycoprotein D gene with antigen-encoding sequences. This single vector platform can be adapted to target various pathogens, providing universal functionality while maintaining reliable immune response generation.
Solution Approach 2:
The invention changes the genetic parameters of the HSV-2 virus by deleting the glycoprotein D gene and inserting heterologous antigen genes. This parameter change allows the vector to express different antigens for various pathogens while maintaining the viral delivery mechanism's reliability in eliciting immune responses.
2Adaptability or versatility
If the HSV-2 glycoprotein D gene is deleted to create a vaccine vector, then the vector can express heterologous antigens, but the virus may have reduced replication capability
Solution Approach 1:
The glycoprotein D gene is extracted (deleted) from the HSV-2 genome to create space for inserting heterologous antigen genes. This extraction allows the vector to express foreign antigens while the virus maintains sufficient replication capability through compensatory mechanisms or by retaining other essential viral genes.
Solution Approach 2:
The heterologous antigen genes are nested within the HSV-2 genome in place of the deleted glycoprotein D gene. This nesting allows the viral vector to carry and express foreign antigen sequences while maintaining the overall viral structure and replication machinery necessary for immune response generation.
3Difficulty of detecting and measuring
If a fluorescent protein marker is used to screen recombinant viruses, then plaques showing fluorescence can be easily identified, but the screening process requires additional equipment and time
Solution Approach 1:
A fluorescent protein marker is used to create a visible color/fluorescence change in plaques that contain the desired recombinant virus. This allows easy visual identification of positive clones under appropriate lighting, significantly simplifying the screening process despite requiring fluorescence detection equipment.
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
This approach enables the production of a vaccine vector that effectively elicits and enhances an immune response, providing protection against influenza and HIV infections by utilizing the HSV-2 vector to express heterologous antigens, thereby addressing the limitations of existing vaccines.
Implementation Method 1
a nucleic acid comprising a promoter-FP construct, wherein FP is a nucleic acid encoding a fluorescent protein; screening plaques resulting from b) to identify plaques not showing fluorescence under excitation light which elicits fluorescent protein fluorescence
Implementation Method 2
a vaccine vector that effectively elicits and enhances an immune response, providing protection against influenza and HIV infections by utilizing the HSV-2 vector to express heterologous antigens
Data Source
AI summary
Recombinant herpes simplex virus 2 (HSV-2) vaccine vectors, compositions and vaccines comprising such, and methods of use thereof are each provided.