Recombinant HSV2 Glycoprotein D Immune Complexes for Cross-Neutralization
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Solution Overview
Problem
Current vaccines for herpesviruses, such as herpes simplex virus type 2 (HSV2), are not effective in inducing a robust immune response and often require multiple doses to achieve the desired immunogenicity, and there is a need for a more efficient vaccination composition that can generate a strong and cross-neutralizing immune response.
Innovation Solution
The development of recombinant immune complexes (RICs) comprising an immunoglobulin heavy chain, an epitope tag, and a fragment of HSV2 glycoprotein D, which form self-multimerizing complexes to enhance immune receptor binding and activation of the complement cascade, leading to a potent immune response.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If traditional immune complexes are used for herpesvirus vaccination, then the vaccine can be administered, but the immune response is weak and multiple doses are required
Solution Approach 1:
The patent creates recombinant immune complexes by fusing antibody heavy chains to viral antigens (such as HSV glycoprotein D), forming composite molecular structures that combine the immunogenicity of the antigen with the immune-binding capability of the antibody. This composite structure enhances immune recognition and response, allowing for more effective single-dose vaccination compared to traditional separate antigen-antibody mixtures
Solution Approach 2:
The invention implements a nested structure where the viral antigen is fused to the C-terminus of the antibody heavy chain, creating an antibody-antigen conjugate that can bind to antigen-specific B cell receptors. This nested arrangement (antigen embedded within the antibody structure) creates a self-multimerizing complex that potently activates B cells and enhances immunogenicity, reducing the need for multiple doses
2Reliability
If live attenuated or genetically modified viruses are used as vaccines, then they can induce specific immune response, but they require complex propagation systems and cell lines
Solution Approach 1:
The patent extracts only the essential immunogenic component (the viral antigen such as glycoprotein D) from the complete virus particle, separating it from the complex propagation requirements of live attenuated vaccines. By using recombinant DNA technology to express just the antigenic protein fused to an antibody, the invention eliminates the need for complex cell line propagation systems while maintaining immune response specificity
Solution Approach 2:
The invention introduces an antibody heavy chain as an intermediary molecule that bridges the viral antigen and the immune system. The antibody portion facilitates B cell recognition and activation through its binding to the antigen, while the fused antigen provides viral specificity. This intermediary structure simplifies production compared to live virus systems while maintaining immunogenicity
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 RICs demonstrate significantly higher immunogenicity and cross-neutralization capabilities against both HSV1 and HSV2, achieving up to 1,000-fold higher antibody titers and neutralization compared to traditional immune complexes, with minimal doses and without adjuvant.
Implementation Method 1
an immunoglobulin heavy chain; an epitope tag (e.g., a 6H epitope tag, etc.), wherein the immunoglobulin heavy chain binds the epitope tag
Data Source
AI summary
Provided herein is a vaccination composition that comprises a recombinant immune complex (RIC) that includes an immunoglobulin heavy chain; an epitope tag, wherein the immunoglobulin heavy chain binds the epitope tag; and at least a fragment of a herpes simplex virus (HSV) type 2 glycoprotein D (HSV2 glycoprotein D). Related methods, recombinant vectors, and other aspects are also provided.