Particle-Displayed Vaccine Composition for Large Antigens
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current vaccine development methods struggle to effectively express large or multicomponent antigens, leading to inadequate immune responses against pathogens like HCMV and RSV, as they often rely on separate expression and packaging of components or short peptides that fail to represent the native pathogen, resulting in antigenically variable pathogens and limited immunogenicity.
Innovation Solution
A composition comprising a protein component linked via an isopeptide bond between first and second peptide tags, allowing for the display of large or multicomponent antigens on particles such as VLPs, ensuring correct orientation and conformation for robust immune response induction.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of manufacture
If large or multicomponent antigens are expressed using traditional separate packaging methods, then manufacturing complexity is reduced, but immune response efficacy deteriorates due to inability to maintain correct orientation and conformation
Solution Approach 1:
The large antigen is divided into multiple smaller subunits that can be separately expressed and purified, then assembled into VLPs with correct orientation through peptide tag-mediated isopeptide bonds. This segmentation allows manageable manufacturing while preserving immunogenicity.
Solution Approach 2:
Multiple antigen subunits are nested within and assembled onto the VLP structure, creating a hierarchical organization where smaller protein components are integrated into the larger viral particle framework, enabling correct spatial arrangement and conformation.
2Ease of manufacture
If short peptides are used as antigens, then manufacturing complexity is reduced, but immunogenicity deteriorates due to antigenic variability and inability to represent native pathogen
Solution Approach 1:
The vaccine combines multiple peptide antigens with VLP structural components to create a composite immunogen. The peptides are displayed on the VLP surface in a geometrically repetitive array, enhancing immunogenicity while maintaining manufacturing advantages of peptide synthesis.
Solution Approach 2:
Short peptides are transformed from linear sequences into three-dimensional structures by displaying them on the surface of spherical VLPs. This dimensional transformation allows the peptides to be presented in a native-like conformation and geometric arrangement, significantly improving immunogenicity.
3Adaptability or versatility
If multiple components are packaged separately, then manufacturing flexibility is improved, but immune response deteriorates due to lack of geometrically repetitive array presentation
Solution Approach 1:
Multiple separately manufactured antigen components are merged onto a single VLP platform through peptide tag attachment. This combining step creates a unified immunogen that presents all antigens in a geometrically repetitive array, leveraging the immunogenic advantages of repetitive structures while retaining manufacturing flexibility.
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 approach enables the generation of a clinically significant immune response by presenting large/multicomponent antigens in a geometrically repetitive array, enhancing immunogenicity and neutralizing capability against pathogens like HCMV and RSV.
Implementation Method 1
a protein component and a moiety are linked via an isopeptide bond between said first and second peptide tags
Data Source
AI summary
The present invention relates to vaccine compositions, most notably vaccine compositions wherein the antigenic component is large, for example over 50 kDa, or multimeric, i.e. comprised of subunits. Such antigenic components are of particular interest, because they may represent antigenic components from pathogens that currently it is not possible to vaccinate against. The invention relates to a composition comprising a particle displaying an antigenic component, wherein said composition comprises an antigenic component comprising a first peptide tag, and a moiety comprising a second peptide tag, wherein the antigenic component and the moiety are linked via an isopeptide bond between said first and second peptide tags, and wherein the antigenic component is over 50 kDa, or alternatively is multimeric.