Immunogenic Nanoparticle Constructs with Cationic Polymer Coatings
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
There is an urgent need for safe and effective therapeutic and prophylactic agents against emerging infectious diseases such as COVID-19, particularly for inducing immune responses against beta-coronaviruses like SARS-CoV-2, as well as other infectious diseases like Dengue fever and malaria.
Innovation Solution
The development of immunogenic constructs comprising nanoparticles coated with cationic polymers and stabilizers, combined with antigens or antigen-producing agents like mRNA, and adjuvants such as CpG oligonucleotides, to induce immune responses. These constructs can be administered intramuscularly to stimulate antigen-presenting cells and activate immune cells, enhancing both cellular and humoral immunity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If traditional vaccine formulations are used, then manufacturing and administration are simpler, but immune response potency and duration are insufficient for emerging infectious diseases
Solution Approach 1:
The patent combines multiple functional components (antigen, adjuvant, nanoparticle carrier, cationic polymer, stabilizer) into a single integrated immunogenic construct. This merging allows the construct to provide both potent immune stimulation and sustained antigen delivery, resolving the contradiction between immune response potency and construct complexity by achieving multiple functions in one unified system.
Solution Approach 2:
The immunogenic construct uses composite material architecture where a nanoparticle core is coated with cationic polymer and stabilizer layers, and loaded with antigen and adjuvant. This composite structure enables controlled antigen release, enhanced stability, and improved immune cell uptake, thereby increasing immune response potency while maintaining manufacturability through established nanotechnology platforms.
2Reliability
If high doses of antigen are administered to ensure adequate immune response, then immune coverage is improved, but side effects and immune system overload increase
Solution Approach 1:
The adjuvant is incorporated into the construct to pre-activate antigen-presenting cells before antigen delivery. This preliminary action primes the immune system to respond more efficiently to lower antigen doses, achieving adequate immune coverage without requiring high antigen amounts that would cause side effects or immune system overload.
Solution Approach 2:
The nanoparticle carrier changes the physical and chemical parameters of antigen delivery, including size, surface charge, and release kinetics. These parameter changes enhance antigen uptake by immune cells and prolong antigen persistence at the injection site, allowing effective immune coverage with reduced antigen doses and minimized side effects.
3Duration of action of stationary object
If antigen is delivered without sustained release mechanism, then administration is simpler, but immune response duration is insufficient for long-lasting immunity
Solution Approach 1:
The nanoparticle carrier employs a porous structure that enables controlled and sustained antigen release over time. The porous architecture provides large surface area for antigen loading while allowing gradual diffusion of antigen to immune cells, thereby extending the duration of immune stimulation and achieving long-lasting immunity without requiring complex multi-dose regimens.
Solution Approach 2:
The construct delivers antigen in a sustained manner that exceeds the minimum required dose over an extended period. This partial or excessive action ensures adequate immune stimulation throughout the immune response timeline, maintaining immunity duration without requiring overly complex delivery systems through optimized nanoparticle formulations.
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 immunogenic constructs effectively induce potent and long-lasting immunity against infectious agents, including beta-coronaviruses, by activating immune cells and producing antibodies, thereby preventing future infections or reducing disease severity.
Implementation Method 1
a crosslinked cationic polymer bound to an exterior surface of the nanoparticle
Implementation Method 2
a stabilizer bound to the crosslinked cationic polymer or the exterior surface of the nanoparticle
Data Source
AI summary
Disclosed are immunogenic constructs including: a nanoparticle; a cationic polymer electrostatically bound to an exterior surface of the nanoparticle and a stabilizer bound to the cationic polymer or the exterior surface of the nanoparticle; and an antigen or antigen producing agent. Optionally, the constructs may include adjuvant and/or one or more functional oligonucleotide(s) (e.g., siRNA or pDNA). Also disclosed are methods of using the provided immunogenic constructs for co-delivering an adjuvant, antigen, and optionally siRNA to a cell, inducing immune response in a subject, and treating or preventing an infectious disease in a subject.