Sublingual Adjuvants Inducing Antigen-Specific Tolerance
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Solution Overview
Problem
Current adjuvants for sublingual immunotherapy do not effectively induce antigen-specific tolerance and may have toxic effects, failing to adequately enhance the host immune response and trigger T-cell mediated active tolerance mechanisms.
Innovation Solution
The use of a lactic acid bacterium, such as Lactobacillus plantarum, or a combination of a corticosteroid with vitamin D3 or its metabolites, administered sublingually or orally, to elicit antigen-specific regulatory T cells, which inhibit Th1 and Th2 effector mechanisms by increasing IL10 secretion.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Power
If conventional adjuvants (saponins, pluronic polymers, mycobacteria, Freund's adjuvant, LPS, lipid A, liposomes) are used to enhance immune response, then the host immune response is potentiated, but toxic effects occur
Solution Approach 1:
The patent changes the chemical and biological parameters of adjuvants by using biologically derived substances (bacterial cell walls from Lactobacillus plantarum and Bifidobacterium species, and vitamin D3 analogs) instead of conventional synthetic or killed bacterial adjuvants. These parameter changes maintain immunostimulatory activity while reducing toxicity through natural biodegradability and selective immune modulation.
Solution Approach 2:
The patent employs biologically derived adjuvants that are naturally degradable and transient in the body, replacing persistent conventional adjuvants. The bacterial cell wall components and vitamin D3 analogs are metabolized and eliminated naturally, avoiding long-term accumulation and chronic toxicity while providing sufficient acute immunostimulatory effect.
2Power
If adjuvants are used to trigger T-cell mediated immune effector mechanisms, then immune response is enhanced, but antigen-specific tolerance is not established
Solution Approach 1:
The patent inverts the conventional adjuvant approach by using substances that preferentially induce regulatory T cells (Tr1 and Th3) rather than effector T cells. Instead of triggering Th1/Th2 effector mechanisms, the adjuvants (bacterial cell walls and vitamin D3 analogs) activate IL-10 and TGF-beta production, thereby inverting the immune response direction toward tolerance induction while maintaining antigen specificity.
Solution Approach 2:
The patent changes the immunological parameters by selecting adjuvants that specifically modulate T cell differentiation toward regulatory phenotypes. The bacterial cell wall components and vitamin D3 analogs alter the cytokine milieu and signaling pathways to favor Foxp3+ Treg and IL-10 producing Tr1 cell development, thereby changing the quality of immune response from effector to regulatory.
3Object-affected harmful factors
If sublingual immunotherapy is used to treat allergies, then safety is improved compared to subcutaneous route, but efficacy in inducing tolerance is insufficient
Solution Approach 1:
The patent introduces adjuvants (bacterial cell walls and vitamin D3 analogs) as intermediaries in sublingual immunotherapy to bridge the gap between safety and efficacy. These adjuvants act as mediators that enhance antigen presentation and regulatory T cell activation at the sublingual mucosal site, thereby improving tolerance induction efficacy without compromising the safety advantages of the sublingual route.
Solution Approach 2:
The patent creates composite immunotherapeutic formulations by combining allergens with immunomodulatory adjuvants (bacterial cell wall components and vitamin D3 analogs). This composite approach synergistically enhances the sublingual immunotherapy effect, where the adjuvants amplify the tolerance-inducing capability of the allergen while maintaining the non-invasive safety profile of sublingual administration.
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
These adjuvants improve the clinical efficacy of immunotherapy by inducing antigen-specific tolerance, reducing immune responses to allergens, and are particularly effective in treating allergies and autoimmune diseases.
Implementation Method 1
the allergen is captured within the oral mucosa by Langerhans-like dendritic cells expressing high affinity IgE receptors
Implementation Method 2
These T-cell mediated regulatory mechanisms inhibit the above mentioned Th1 and Th2 effector mechanisms, in particular by eliciting an increase in IL10 secretion by T cells
Data Source
Figure 1A
Figure 1B
Figure 2A~2B
AI summary
The invention relates to an immunogenic composition for sublingual, perlingual or oral administration, comprising at least an antigen and at least an adjuvant that is a bacterium selected from a Bifidobacterium and a lactic acid bacterium, or a combination of a corticosteroid with vitamin D3 or any metabolite or analog of the latter, in a pharmaceutically acceptable carrier that is suitable for sublingual, perlingual, or oral administration. Such compositions allow to elicit antigen-specific immune tolerance.