Recombinant Poxvirus Vector Fused with Tetanus Toxin Fragment C
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Solution Overview
Problem
Current recombinant virus vectors, particularly poxviruses, face challenges in effectively expressing bacterial antigens and eliciting an immune response, as they lack mechanisms to enhance the immunogenicity of antigens and overcome difficulties in protein expression and antibody production.
Innovation Solution
Incorporating a tetanus toxin fragment C (TTC) coding sequence operably linked to a bacterial antigenic determinant coding sequence within recombinant poxvirus vectors, which enhances antibody response and immunogenicity by acting as an immunostimulant, regardless of the administration route, and allows for correct protein folding and post-translational modifications.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If a recombinant poxvirus vector expresses a bacterial antigen alone, then the antigen can be delivered to the host, but the immune response is weak and insufficient for effective vaccination
Solution Approach 1:
The patent combines the bacterial antigen coding sequence with the tetanus toxin fragment C coding sequence to create a fusion protein. This merging allows the antigen to benefit from the immunostimulatory properties of TTC while maintaining its own immunogenicity, resulting in enhanced antibody production and immune response effectiveness that neither component achieves alone.
Solution Approach 2:
Tetanus toxin fragment C acts as an intermediary that mediates enhanced immune response. When fused to the bacterial antigen, TTC serves as a carrier that stimulates the immune system more effectively, leading to increased antibody titers and improved seroconversion rates compared to the antigen expressed alone.
2Quantity of substance
If multiple copies of the antigen are used to enhance immune response, then antibody titer increases, but the vector complexity and difficulty of expression increase
Solution Approach 1:
Instead of increasing the number of antigen copies, the patent changes the molecular parameters of the antigen by fusing it to TTC. This parameter change (adding the immunostimulatory TTC component) enhances the immune response per unit of antigen, achieving high antibody titers without increasing vector complexity or requiring multiple antigen copies.
3Productivity
If strong promoters are used to increase antigen expression, then more antigen is produced, but the expression system becomes more complex and harder to control
Solution Approach 1:
The patent creates a composite protein structure by fusing the bacterial antigen with TTC. This composite approach enhances the immunogenicity and expression efficiency of the antigen without requiring strong promoters or complex expression systems. The fusion protein leverages the properties of both components to achieve high expression levels with a simple, controllable system.
4Reliability
If bacterial proteins are expressed in bacterial host cells, then expression success is high, but the applicability to viral vector systems is limited
Solution Approach 1:
The patent demonstrates that the TTC-fusion strategy, originally developed for bacterial expression systems, can be universally applied to viral vector systems like poxviruses. This multi-functional approach allows the same fusion protein strategy to work across different host systems (bacterial and viral), enhancing both reliability of expression and adaptability to various vaccine platforms.
Data Source
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AI summary
The present invention relates to a recombinant poxvirus comprising tetanus toxin fragment C for improved immunogenicity of an antigen and related methods and uses. Specifically, the present invention generally relates to genetically engineered (recombinant) poxvirus vectors comprising a tetanus toxin fragment C (TTC) coding sequence operably linked to a bacterial antigenic determinant as well as to uses thereof, e.g., to affect an immune response in a subject.