gD Chimeric Protein Constructs for Stronger CD8+ T Cell Responses
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Solution Overview
Problem
Existing vaccines and immunization strategies fail to effectively stimulate robust CD8+ T cell responses against heterologous antigens, particularly in the presence of pre-existing immunity or when using certain viral vectors.
Innovation Solution
Development of chimeric proteins by inserting heterologous antigens into the C-terminal region of the herpesvirus glycoprotein D (gD), which enhances immune response by interacting with HVEM and disrupting the HVEM-BTLA pathway, thereby stimulating CD8+ T cell responses.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If existing vaccines and immunization strategies are used, then general immunization is achieved, but robust CD8+ T cell responses against heterologous antigens are not effectively stimulated
Solution Approach 1:
The patent combines the herpesvirus glycoprotein D (gD) carrier protein with heterologous antigens to create chimeric proteins. This merging allows the vaccine to leverage the proven immunogenicity of gD while presenting new heterologous antigens, thereby achieving robust CD8+ T cell responses against antigens that would otherwise fail to elicit strong immune responses when administered alone.
Solution Approach 2:
The gD protein serves as an intermediary carrier that mediates the presentation of heterologous antigens to the immune system. By fusing heterologous antigens to gD, the patent creates a bridge that allows the immune system to recognize and respond to new antigens through the established gD immunization pathway, overcoming the limitation of poor responses to heterologous antigens.
2Reliability
If pre-existing immunity is present, then prior immune protection exists, but stimulation of new CD8+ T cell responses is inhibited
Solution Approach 1:
The patent segments the immune response pathway by using gD as a separate carrier component that independently stimulates immune cells through its known receptors (HVEM and nectins). This segmentation allows the heterologous antigen to be presented alongside the gD carrier, enabling new T cell responses to be generated even in the presence of pre-existing immunity, as the gD portion can still effectively engage immune cell receptors.
3Reliability
If certain viral vectors are used, then delivery mechanism is established, but effective immune stimulation is reduced
Solution Approach 1:
The gD-based chimeric protein system serves multiple functions: it acts as a carrier for heterologous antigens, provides its own immunogenicity, and can be delivered through various platforms (DNA vaccines, viral vectors, protein formulations). This multi-functionality reduces dependency on specific viral vectors and allows the same chimeric construct to be used across different delivery systems, thereby improving reliability while reducing vector-specific complexity.
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
The chimeric proteins significantly enhance CD8+ T cell responses to the inserted antigens, providing improved immunogenicity and therapeutic or prophylactic efficacy, especially in the presence of pre-existing immunity or when using specific viral vectors.
Implementation Method 1
gD interacts with two alternative receptors belonging to unrelated protein families, the herpesvirus entry mediator (HVEM) and the nectins
Data Source
AI summary
The instant disclosure provides chimeric protein constructs which comprise a herpesvirus glycoprotein D (gD) and a heterologous polypeptide that interacts with herpes virus entry mediator (HVEM) which enhances immune responses directed against the heterologous polypeptide. Also provided are compositions and methods of enhancing an immune response and treating a disease or disorder comprising said chimeric protein constructs.