Self-Assembling KARI Nanoparticles for Multivalent Antigen Display
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Solution Overview
Problem
Current vaccine designs lack effectiveness against various SARS-CoV-2 variants, highlighting the need for more potent and universal therapeutic or vaccine solutions to combat the COVID-19 pandemic.
Innovation Solution
Development of a self-assembling nanoparticle composed of a recombinant Ketol-acid reductoisomerase (KARI) with a tether sequence, operably linked to proteins or peptides of interest, such as antigens, to create an immunogenic conjugate for enhanced immune response.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional vaccine designs are used, then vaccine development can proceed with existing platforms, but effectiveness against various SARS-CoV-2 variants is insufficient
Solution Approach 1:
The nanoparticle platform is designed to display multiple different antigens (SARS-CoV-2 spike protein, influenza hemagglutinin, and other viral antigens) simultaneously on a single particle surface, enabling a single vaccine to provide protection against multiple pathogens and variants. This multi-valent approach allows the vaccine to adapt to different viral threats without requiring complete redesign of the platform.
Solution Approach 2:
The patent employs stabilized versions of viral envelope proteins with modified amino acid sequences that enhance thermal stability and conformational stability. These parameter changes in protein stability ensure that the antigens maintain their immunogenic conformation under various storage and physiological conditions, improving vaccine reliability across different variants.
2Reliability
If VLPs are used for antigen display, then strong immune responses can be elicited, but the complexity of identifying and engineering novel self-assembling molecules increases
Solution Approach 1:
The patent uses a self-assembling protein scaffold (such as ferritin or other nanocages) as an intermediary structure that naturally forms stable nanoparticles. This scaffold serves as a pre-engineered platform that automatically organizes antigens in optimal configurations, eliminating the need to de novo engineer complex self-assembling molecules for each new antigen or variant.
Solution Approach 2:
The vaccine design separates the nanoparticle platform from the antigen components. The self-assembling scaffold forms the structural core, while antigens are attached as modular units on the surface. This segmentation allows independent optimization of the scaffold structure and antigen selection, reducing overall engineering complexity.
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 nanoparticle design elicits strong and long-lasting immune responses, providing a potential solution for vaccines against SARS-CoV-2 variants and other viral pathogens by stabilizing and optimizing antigen presentation.
Implementation Method 1
a self-assembling nanoparticle comprising, consisting of, consisting essentially of an amino acid sequence of a recombinant Ketol-acid reductoisomerase (KARI; EC 1.1.1.86)
Data Source
AI summary
This disclosure provides self-assembling Ketol-acid reductoisomerase (KARI) nanoparticles that are capable of displaying multiple copies of antigens, antibodies and/or proteins or peptides on its surface; as well as nucleic acids encoding recombinant KARI molecules, vectors expressing recombinant KARI molecules, immunogenic polypeptides comprising the self-assembling KARI nanoparticles, methods of producing the self-assembling KART nanoparticles, and methods for eliciting an immune response against an antigen in a subject comprising the self-assembling KARI nanoparticles.