Multi-antigen Fusion Protein for CD8+ T Cell Stimulation

Resolve Bottlenecks,
Find Innovative Solutions
Generate Solutions

Solution Overview

Problem

Current vaccines lack effectiveness in stimulating CD8+ T cell immunity, are costly to produce, and face challenges in quality control, with existing methods either inefficient or associated with side effects, and there is a need for a vaccine that can safely and easily stimulate both CD4+ and CD8+ T cell responses.

Innovation Solution

An artificial multi-antigen fusion protein is developed, comprising multiple antigen segments connected by cathepsin cleavage sites, which can be presented to MHC-I molecules, effectively stimulating CD8+ T cells and retaining the ability to stimulate CD4+ T cells, thereby overcoming the limitations of existing vaccines.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Adaptability or versatility

If multiple polypeptides are used to cover all T cell epitopes, then epitope coverage is improved, but production cost and quality control complexity increase

Engineering Contradiction:
Improveepitope coverageVSAvoidproduction process complexity
Core Design Contradiction:
Adaptability or versatilityVSDevice complexity

Solution Approach 1:

The patent combines multiple T cell epitopes (both CD4+ and CD8+ epitopes) into a single fusion protein construct. This merging approach maintains comprehensive epitope coverage while simplifying production to a single protein expression and purification process, eliminating the need to produce and quality control multiple separate polypeptides

Inventive Principle:
Principle #5Merging (Combining)

Solution Approach 2:

The fusion protein is designed to simultaneously serve multiple functions: it presents both CD4+ and CD8+ T cell epitopes, enables comprehensive epitope coverage, and simplifies production. The single protein construct performs the work of multiple polypeptides while reducing manufacturing complexity

Inventive Principle:
Principle #6Universality (Multi-functionality)

2Ease of manufacture

If a limited number of polypeptides are selected to reduce cost, then production cost is reduced, but epitope coverage is reduced

Engineering Contradiction:
Improveproduction costVSAvoidepitope coverage
Core Design Contradiction:
Ease of manufactureVSAdaptability or versatility

Solution Approach 1:

The patent merges multiple epitopes into a single fusion protein, achieving comprehensive epitope coverage with a single production process. This approach reduces the number of separate polypeptide productions needed while maintaining complete epitope representation, thereby reducing overall production cost

Inventive Principle:
Principle #5Merging (Combining)

3Reliability

If traditional vaccines are used to stimulate CD8+ T cells, then CD8+ T cell stimulation is improved, but safety and production complexity worsen

Engineering Contradiction:
ImproveCD8+ T cell stimulation effectivenessVSAvoidproduction complexity
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The patent segments the vaccine into distinct epitope regions within a fusion protein, including CD8+ epitopes that can be presented by MHC class I molecules and CD4+ epitopes for MHC class II presentation. This segmentation allows effective CD8+ T cell stimulation through specific epitope presentation while maintaining a simpler production process compared to traditional complex vaccines

Inventive Principle:
Principle #1Segmentation

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 fusion protein efficiently stimulates CD8+ T cells through the MHC-I pathway while maintaining CD4+ T cell stimulation, reducing production costs and simplifying quality control, and demonstrates improved immune response compared to traditional vaccines.

Implementation Method 1

The fusion protein of the present invention can be phagocytosed by antigen presenting cells and activate CD8+ cells

Methodology Applied
Scientific EffectPhagocytosis:

Implementation Method 2

a series of long peptides containing antigen segment are ligated by recognition sequences of cathepsin in the endosome and lysosome of antigen presenting cells

Methodology Applied
Scientific EffectLysosomal degradation: Decomposition (biological)

Implementation Method 3

the fusion protein vaccine... can be presented to MHC-I molecules, effectively stimulating CD8+ T cells

Methodology Applied
Scientific EffectMHC-I antigen presentation:

Data Source

PatentUS11833220B2Artificial multi-antigen fusion protein and preparation and use thereof
Publication Date: 2023.12.05 OXFORD VACMEDIX (UK) LTD
  • US11833220B2 patent drawing
  • US11833220B2 patent drawing
  • US11833220B2 patent drawing

AI summary

Provided are an artificial multi-antigen fusion protein and a preparation method thereof. The fusion protein can effectively stimulate CD8+T and CD4+ T cell immunities, and can be applied to immunodiagnostics or serve as a prophylactic or therapeutic vaccine.