Adjuvant-Loaded Nanoparticles for Mucosal Immunity

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Solution Overview

Problem

Current vaccines primarily target the systemic immune system after pathogens have crossed mucosal barriers, offering incomplete protection and sometimes causing infectious pathologies, especially in immune-compromised individuals, and fail to induce long-lasting immunity at mucosal surfaces.

Innovation Solution

Development of vaccine compositions comprising inactivated pathogens attached to adjuvant-loaded polymeric nanoparticles, specifically targeting mucosal membranes with Toll-like receptor agonists like R848, monophosphoryl lipid A, or unmethylated CpG oligodeoxynucleotides, administered through mucosal routes to stimulate mucosal immunity.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If vaccines target the systemic immune system after pathogens cross mucosal barriers, then systemic immunity is activated, but protection is incomplete and infectious pathologies may occur

Engineering Contradiction:

Improveimmune protectionVSAvoidinfectious pathologies

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The vaccine composition acts preemptively at the mucosal barrier before pathogens can cross into the systemic environment. By delivering adjuvants and antigens directly to mucosal surfaces, the system activates local immune responses in advance, preventing pathogen invasion rather than responding after crossing occurs.

Inventive Principle:

Principle #10Preliminary action

Solution Approach 2:

Polymeric nanoparticles serve as intermediary carriers that deliver adjuvants and antigens to mucosal surfaces. These nanoparticles facilitate targeted delivery to mucosal-associated lymphoid tissue, enabling localized immune activation without requiring systemic distribution, thus avoiding systemic side effects while maintaining protective efficacy.

Inventive Principle:

Principle #24Intermediary (Mediator)

2Object-affected harmful factors

If inactivated pathogens are used to avoid infectious pathologies, then safety is improved, but long-lasting mucosal immunity is not induced

Engineering Contradiction:

Improveinfectious pathologiesVSAvoidimmunity duration

Core Design Contradiction:

Object-affected harmful factorsVSDuration of action of moving object

Solution Approach 1:

The patent modifies the physical and chemical parameters of antigen delivery by using polymeric nanoparticles. These nanoparticles control the release kinetics of adjuvants and antigens, providing sustained local concentrations that prolong immune stimulation at the mucosal surface, thereby generating long-lasting immunity without requiring live pathogens.

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The vaccine composition combines inactivated pathogens with adjuvant-loaded polymeric nanoparticles, creating a composite system. This composite approach integrates the safety of inactivated pathogens with the immunoenhancing properties of adjuvants delivered via nanoparticles, achieving both safety and prolonged mucosal immunity.

Inventive Principle:

Principle #40Composite materials

3Reliability

If adjuvants are loaded into polymeric nanoparticles for targeted delivery, then mucosal immunity is enhanced, but composition complexity increases

Engineering Contradiction:

Improvemucosal immunityVSAvoidcomposition structure

Core Design Contradiction:

ReliabilityVSDevice complexity

Solution Approach 1:

The polymeric nanoparticle system performs multiple functions simultaneously: it serves as an antigen carrier, an adjuvant delivery vehicle, and a targeting mechanism for mucosal surfaces. This multi-functionality consolidates what would otherwise require separate components into a single integrated platform, managing complexity while enhancing mucosal immunity.

Inventive Principle:

Principle #6Universality (Multi-functionality)

Solution Approach 2:

Adjuvants are encapsulated within the polymeric nanoparticle structure, creating a nested configuration where the adjuvant is contained within the polymer matrix. This nesting approach allows controlled release and targeted delivery while maintaining a compact, manageable composition structure.

Inventive Principle:

Principle #7Nested doll (Nesting)

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 compositions induce robust, long-lasting mucosal immunity, preventing initial colonization and replication of pathogens, and provide complete immune protection by targeting the mucosal membranes, thereby enhancing protective immunity against infections.

Implementation Method 1

The one or more adjuvant-loaded polymeric nanoparticles are attached to the inactivated pathogen through electrostatic attraction

Methodology Applied

Scientific EffectElectrostatic attraction: Electrostatics

Data Source

PatentEP2968510B1Nanoparticle-based compositions

Publication Date: 2019.10.09 PRESIDENT & FELLOWS OF HARVARD COLLEGE

Figure 1A~1B
Figure 1C~1F
Figure 2A~2E

AI summary

Provided herein are new compositions including an inactivated pathogen and one or more adjuvant-loaded polymeric nanoparticles, wherein the adjuvant-loaded nanoparticles are bound to the inactivated pathogen. These compositions are useful for preventing and/or treating diseases caused by the specific pathogens, especially when administered to a subject's mucosal membranes.