Immunogenic Complex via Dialdehyde Crosslinking for Vaccine Design

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Solution Overview

Problem

Current methods for producing vaccines based on polymerized and mannosylated antigens face challenges in effectively polymerizing antigens while preserving mannose structural integrity and maintaining low allergenicity, leading to reduced immunogenicity due to inefficient uptake by dendritic cells.

Innovation Solution

A method involving the addition of a dialdehyde to a mixture of protein antigens and mannan, allowing simultaneous polymerization and conjugation, forming an immunogenic complex covalently crosslinked by a diimine group, which enhances immune response stimulation without triggering allergic reactions and improves dendritic cell recognition.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Object-affected harmful factors

If antigens are polymerized using dialdehyde to reduce allergenicity, then the capacity to react with IgE antibodies is reduced, but the access of mannose receptors in dendritic cells to mannose residues is also reduced, leading to decreased immunogenicity

Engineering Contradiction:
ImproveallergenicityVSAvoidimmunogenicity
Core Design Contradiction:
Object-affected harmful factorsVSReliability

Solution Approach 1:

Mannan acts as an intermediary carrier that presents polymerized antigens to dendritic cells through mannose receptors. The mannan polymer provides accessible mannose residues that serve as recognition markers for DC uptake, while the attached antigen polymer maintains reduced allergenicity. This mediator resolves the contradiction by providing an alternative pathway for antigen delivery that bypasses the limitation imposed by antigen polymerization on direct mannose receptor binding.

Inventive Principle:
Principle #24Intermediary (Mediator)

2Object-affected harmful factors

If chemical modifications are applied to allergens to reduce allergenicity, then reactivity with IgE antibodies is reduced, but immunogenicity may also be reduced

Engineering Contradiction:
ImproveallergenicityVSAvoidimmunogenicity
Core Design Contradiction:
Object-affected harmful factorsVSReliability

Solution Approach 1:

The invention creates a composite structure consisting of mannan polymer conjugated to antigen polymer. This composite material combines the benefits of both components: the mannan provides immunogenicity through mannose receptor recognition, while the antigen polymer provides hypoallergenic properties. The composite structure allows simultaneous achievement of reduced allergenicity and maintained immunogenicity, resolving the contradiction between these two properties.

Inventive Principle:
Principle #40Composite materials

3Object-affected harmful factors

If allergens are polymerized to form allergoids with lower allergenicity, then the number of sensitized mast cells activated is reduced, but the clinical efficacy of vaccines may be reduced due to loss of immunogenicity

Engineering Contradiction:
ImproveallergenicityVSAvoidclinical efficacy
Core Design Contradiction:
Object-affected harmful factorsVSProductivity

Solution Approach 1:

Mannan serves as an intermediary that enhances the clinical efficacy of polymerized allergens by providing an alternative recognition pathway for dendritic cells. The mannan carrier with exposed mannose residues compensates for the reduced immunogenicity of polymerized antigens, ensuring adequate immune stimulation while maintaining the hypoallergenic properties of the antigen polymer.

Inventive Principle:
Principle #24Intermediary (Mediator)

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 method enables the creation of an immunogenic complex that effectively stimulates an immune response with reduced allergic reactions, improving antigen uptake by dendritic cells and increasing immunogenicity, making it suitable for vaccine development.

Implementation Method 1

a polymerized antigen of protein nature covalently crosslinked to a mannan by a diimine group

Methodology Applied
Scientific EffectCovalent crosslinking: Chemical Bonding

Implementation Method 2

based on the antigen and mannan simultaneous polymerization and conjugation by using a dialdehyde

Methodology Applied
Scientific EffectCondensation reaction: Chemical Bonding

Data Source

PatentEP2982381B1Immunogenic complex for vaccination and method for the production thereof
Publication Date: 2020.12.02 INMUNOTEK
  • EP2982381B1 patent drawingFigure 1
  • EP2982381B1 patent drawingFigure 2
  • EP2982381B1 patent drawingFigure 3~4

AI summary

The invention relates to an immunogenic complex comprising a polymerised antigen, mannan and a dialdehyde, to the composition containing same, and to the use thereof as a stimulator of the immune response and a vaccine, useful in the treatment of infectious diseases, neoplasia and allergies. The invention also relates to the method for producing said immunogenic complex, based on the simultaneous polymerisation and conjugation of the antigen and the mannan by means of the use of a dialdehyde.