Self-Assembling Protein Nanostructures for Multivalent Antigen Display
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Solution Overview
Problem
Subunit vaccines often elicit a weaker immune response compared to whole virus or live attenuated vaccines, limiting their effectiveness in generating a robust and broad immune response against pathogens like respiratory syncytial virus (RSV).
Innovation Solution
Development of nanostructures comprising self-assembling polypeptides that multivalently display paramyxovirus and pneumovirus F proteins, forming symmetrically ordered arrays to enhance antigen presentation and immune response potency.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If subunit vaccines are used, then safety is improved (no live pathogen), but immune response potency deteriorates (weaker immune response)
Solution Approach 1:
The vaccine is segmented into multiple identical antigen copies displayed on separate nanostructure units, each capable of independently binding antibodies. This segmentation allows the antigen to be presented in a modular fashion that enhances immune recognition while maintaining the safety of subunit vaccines.
Solution Approach 2:
Multiple copies of the antigen are merged onto a single nanostructure platform, creating a multivalent display system. This merging concentrates multiple antigenic determinants in close proximity, thereby enhancing the overall immune response potency while retaining the safety profile of purified subunit antigens.
2Power
If antigen is displayed in symmetrically ordered arrays, then immune response potency is improved, but manufacturing complexity increases
Solution Approach 1:
The nanostructure employs a universal self-assembling peptide framework that can accommodate different antigens through modular fusion protein design. This universal platform approach simplifies manufacturing by using the same core assembly mechanism across different vaccine candidates, reducing overall manufacturing complexity despite the sophisticated antigen display architecture.
Solution Approach 2:
The nanostructure utilizes self-assembly of purified peptides to form the symmetrically ordered arrays, eliminating the need for complex external assembly equipment or processes. The peptides automatically organize into the desired symmetric structures through their inherent physical-chemical properties, thereby reducing manufacturing complexity.
3Quantity of substance
If multiple copies of antigen are displayed, then antigen presentation is improved, but structural complexity increases
Solution Approach 1:
The antigen is nested within the nanostructure framework as a fusion protein, where the antigen sequence is embedded within the self-assembling peptide sequence. This nesting allows multiple antigen copies to be displayed on the nanostructure surface while maintaining a relatively simple overall structural organization based on repeated modular units.
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 nanostructures increase the potency and breadth of the vaccine-induced immune response, providing improved protection against RSV and potentially other paramyxoviruses by displaying multiple copies of F proteins on their surface, enhancing antibody generation and stability.
Implementation Method 1
wherein the plurality of first assemblies non-covalently interact with the plurality of second assemblies to form a nanostructure
Implementation Method 2
self-assembling polypeptides that multivalently display paramyxovirus and pneumovirus F proteins, forming symmetrically ordered arrays
Data Source
AI summary
Disclosed herein are nanostructures and their use, where the nanostructures include a plurality of first assemblies, each first assembly comprising a plurality of identical first polypeptides selected from 153_dn5A, 153_dn5A.1 and I53_dn5A.2, or variants thereof; and a plurality of second assemblies, each second assembly comprising a plurality of identical second polypeptides being 153 dn5B or a variant thereof, wherein the plurality of first assemblies non-covalently interact with the plurality of second assemblies to form a nanostructure; and wherein the nanostructure displays multiple copies of one or more paramyxovirus and/or pneumovirus F proteins, or antigenic fragments thereof.