Modified Alphavirus VLPs for Higher Yield and Immunogenicity

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Solution Overview

Problem

The evolution and spread of alphaviruses and flaviviruses pose significant public health threats due to the absence of effective vaccines or anti-viral therapies, with existing technologies failing to induce robust immune responses against these pathogens.

Innovation Solution

The development of virus-like particles (VLPs) with altered E2 proteins or capsid proteins, particularly at specific amino acid positions, enhances VLP production and induces high-titer neutralizing antibodies, providing a VLP-based vaccine strategy for alphaviruses and flaviviruses, including Chikungunya, Eastern equine encephalitis, and West Nile viruses.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If wild-type alphavirus proteins are expressed, then the natural viral structure is maintained, but VLP production is insufficient or absent

Engineering Contradiction:

ImproveVLP productionVSAvoidVLP structure fidelity

Core Design Contradiction:

ProductivityVSManufacturing precision

Solution Approach 1:

The patent applies parameter changes by modifying specific amino acid residues in the alphavirus E2 protein (such as position 234 in CHIKV E2) to enhance VLP production. These point mutations alter local structural parameters while preserving the overall VLP architecture, enabling improved particle yield without compromising structural fidelity or immunogenicity.

Inventive Principle:

Principle #35Parameter changes

2Productivity

If VLPs are produced with altered proteins, then VLP production is enhanced, but the alteration must be controlled to maintain immunogenicity

Engineering Contradiction:

ImproveVLP productionVSAvoidimmune response consistency

Core Design Contradiction:

ProductivityVSReliability

Solution Approach 1:

The patent employs local quality by introducing mutations at specific, localized positions within the E2 protein (such as amino acid position 234) rather than throughout the entire protein. This targeted approach allows enhancement of VLP production while preserving the critical immunogenic epitopes and overall protein function, ensuring consistent immune responses.

Inventive Principle:

Principle #3Local quality

3Reliability

If existing vaccine technologies are used, then some level of protection is provided, but robust immune responses are not induced

Engineering Contradiction:

Improveprotection levelVSAvoidimmune response strength

Core Design Contradiction:

ReliabilityVSProductivity

Solution Approach 1:

The patent utilizes parameter changes by modifying the E2 protein sequence at specific positions to enhance the immunogenicity of VLPs. These controlled mutations alter physical and chemical parameters of the protein that improve antigen presentation and B-cell activation, thereby inducing higher titers of neutralizing antibodies and more robust protective immunity.

Inventive Principle:

Principle #35Parameter changes

Data Source

PatentUS20250326801A1Virus-like particles and methods of use

Publication Date: 2025.10.23 THE GOVERNMENT OF THE UNITED STATES OF AMERICA AS REPRESENTED BY THE SECRETARY DEPARTMENT OF HEALTH & HUMAN SERVICES

AI summary

The invention features modified alphavirus or flavivirus virus-like particles (VLPs). The invention provides methods, compositions, and kits featuring the modified VLPs. The invention also features methods for enhancing production of modified VLPs for use in the prevention or treatment of alphavirus and flavivirus-mediated diseases. The invention also provides methods for delivering agents to a cell using the modified VLPs.