Genetically Modified Lactococcus Mucosal Antigen Delivery

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Solution Overview

Problem

Current treatments for autoimmune, allergic, and inflammatory diseases are often palliative, immunosuppressive, and associated with adverse effects, with no effective method to induce antigen-specific tolerance without significant side effects.

Innovation Solution

Mucosal delivery of immunodominant antigens by genetically modified Lactococcus lactis microorganisms, which constitutively express and secrete antigens, induces antigen-specific immune tolerance by activating regulatory T cells and modulating cytokine production.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Object-affected harmful factors

If immunosuppressive drugs are used to treat autoimmune and allergic diseases, then immune responses are suppressed, but adverse effects and lack of antigen-specific tolerance occur

Engineering Contradiction:

Improveimmune response suppressionVSAvoidadverse effects

Core Design Contradiction:

Object-affected harmful factorsVSObject-generated harmful factors

Solution Approach 1:

The patent uses genetically modified Lactococcus lactis as an intermediary delivery system to transport antigen-specific peptides to the mucosal immune system. This mediator enables antigen-specific tolerance induction without the broad immunosuppression and adverse effects associated with conventional immunosuppressive drugs.

Inventive Principle:

Principle #24Intermediary (Mediator)

Solution Approach 2:

The invention delivers antigens specifically to the mucosal immune system through Lactococcus lactis, creating localized antigen-specific tolerance at the mucosal level while preserving systemic immune function. This localized approach avoids the global immunosuppression caused by traditional drugs.

Inventive Principle:

Principle #3Local quality

2Reliability

If antigen is delivered systemically by injection, then immune response is activated, but local infiltration of inflammatory cells occurs

Engineering Contradiction:

Improveimmune response activationVSAvoidinflammatory cell infiltration

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

Instead of delivering antigen systemically by injection (which causes inflammatory infiltration), the patent inverts the approach by delivering antigen through the mucosal route using Lactococcus lactis. This reverse delivery method activates immune responses while avoiding inflammatory cell infiltration at injection sites.

Inventive Principle:

Principle #13The other way round (Inversion)

Solution Approach 2:

The patent replaces the mechanical injection method with a biological delivery system (Lactococcus lactis) that naturally transports antigens to the mucosal immune system. This substitution eliminates the traumatic injection process and associated inflammatory responses.

Inventive Principle:

Principle #28Mechanics substitution (Replace mechanical system)

3Object-affected harmful factors

If oral tolerance is induced by antigen administration, then systemic unresponsiveness is achieved, but treatment efficiency is limited compared to combined approach

Engineering Contradiction:

Improvesystemic unresponsivenessVSAvoidtolerance induction efficiency

Core Design Contradiction:

Object-affected harmful factorsVSProductivity

Solution Approach 1:

The patent combines oral antigen administration with genetically modified Lactococcus lactis delivery to enhance tolerance induction efficiency. This merged approach leverages both the oral tolerance mechanism and the targeted mucosal delivery capability of Lactococcus lactis, achieving superior results compared to either method alone.

Inventive Principle:

Principle #5Merging (Combining)

Solution Approach 2:

The invention creates a composite delivery system combining Lactococcus lactis bacteria with antigen-specific peptides. This composite structure enables enhanced stability, targeted delivery, and improved immunogenicity compared to naked antigen administration, thereby increasing tolerance induction efficiency.

Inventive Principle:

Principle #40Composite materials

Data Source

PatentUS10668136B2Treatment of immune disease by mucosal delivery of antigens using genetically modified <i>Lactococcus</i>

Publication Date: 2020.06.02 INTREXON ACTOBIOTICS NV

AI summary

The present invention relates to the treatment of autoimmune and allergic diseases by mucosal delivery by micro-organism, in particular Lactococcus lactis, of secreted immunodominant antigens.