Melanin-antigen complex adjuvant for subunit vaccine immunogenicity

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Solution Overview

Problem

Subunit vaccines, particularly peptide subunit vaccines, are often poorly immunogenic due to the lack of pathogen-derived molecules acting as danger signals, requiring additional adjuvants for effectiveness, and face challenges in inducing CD8+ responses and stability in manufacturing, leading to high costs and limited antigen availability.

Innovation Solution

The use of melanin, formed through oxidative polymerization of melanin precursors, as an adjuvant to enhance the immunogenicity of antigens by complexing with them, thereby improving immune response activation and stability.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Object-affected harmful factors

If subunit vaccines are used to limit side effects, then safety is improved, but immunogenicity deteriorates

Engineering Contradiction:
Improveside effectsVSAvoidimmunogenicity
Core Design Contradiction:
Object-affected harmful factorsVSReliability

Solution Approach 1:

Melanin acts as an intermediary substance that bridges the gap between subunit vaccines and the immune system. It serves as a danger signal mediator that activates pattern recognition receptors (PRRs) on antigen-presenting cells, thereby compensating for the lack of pathogen-derived danger signals in subunit vaccines and restoring immunogenicity without compromising safety

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The invention creates a composite vaccine formulation combining subunit antigens with melanin. This composite structure allows the subunit vaccine to maintain its safety profile while the melanin component provides the necessary immunostimulatory properties, effectively resolving the contradiction between safety and immunogenicity

Inventive Principle:
Principle #40Composite materials

2Reliability

If additional adjuvants are added to subunit vaccines to improve immunogenicity, then immune response is enhanced, but device complexity increases

Engineering Contradiction:
Improveimmune responseVSAvoidformulation complexity
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

Melanin serves multiple functions simultaneously: it acts as a danger signal, activates pattern recognition receptors, enhances antigen presentation, and provides structural stability. This multi-functionality eliminates the need for multiple separate adjuvants, simplifying the formulation while maintaining enhanced immune response

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

Solution Approach 2:

The invention merges the roles of multiple adjuvants into a single melanin component. Instead of combining several different adjuvants to achieve the desired immune response, melanin alone provides all necessary immunostimulatory functions, thereby reducing formulation complexity

Inventive Principle:
Principle #5Merging (Combining)

3Measurement precision

If peptide subunit vaccines are used to focus immune response, then specificity is improved, but immunogenicity deteriorates

Engineering Contradiction:
Improveimmune response specificityVSAvoidimmunogenicity
Core Design Contradiction:
Measurement precisionVSReliability

Solution Approach 1:

Melanin serves as an intermediary danger signal that compensates for the minimal immunogenicity of peptides. The short peptide maintains its specificity for the target antigen while melanin provides the necessary danger signal to activate the immune system, ensuring both specificity and immunogenicity are achieved

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

Melanin acts as a potent adjuvant, increasing the immunogenicity of antigens, reducing the required antigen dose, and enhancing both humoral and cellular immune responses, while being stable and easy to manufacture, thus overcoming the limitations of subunit vaccines.

Implementation Method 1

a melanin macromolecule obtained from the oxidative polymerization of precursors related to indole or cathecol

Methodology Applied
Scientific EffectOxidative polymerization: Oxidation

Data Source

PatentUS11904014B2Immunostimulatory compositions
Publication Date: 2024.02.20 ASSISTANCE PUBLIQUE HOPITAUX DE PARIS (APHP)
  • US11904014B2 patent drawing
  • US11904014B2 patent drawing
  • US11904014B2 patent drawing

AI summary

The invention relates to the use of melanin, complexed with an antigen, as a immunostimulatory composition.