Phage-Displayed scFv Library for Rapid Neutralizing Antibody Screening
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current methods for addressing influenza virus infections, including vaccines and antiviral drugs, are inadequate in providing immediate protection against emerging viral strains, and there is a need for a high-throughput method to screen for neutralizing antibodies that can effectively counter pandemic threats.
Innovation Solution
A method involving a phage-displayed single-chain variable fragment (scFv) library is used, where scFvs with binding affinity to protein A and protein L are exposed to viral antigens, selected under acidic conditions, and their neutralizing efficacy is determined to identify superior neutralizing antibodies, which can be further developed into recombinant antibodies for treatment.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If vaccines and antiviral drugs are used to address influenza virus infections, then protection against known strains is provided, but immediate protection against emerging viral strains is not achieved
Solution Approach 1:
The patent applies preliminary action by pre-construction of a large diverse phage-displayed scFv library before pandemic outbreaks occur. This library contains antibodies with varying specificities that can be rapidly screened against emerging viral strains, eliminating the need for de novo antibody generation during crises.
Solution Approach 2:
The patent employs parameter changes by selecting scFvs under acidic conditions (pH 5.0) during screening, which mimics the endosomal environment where influenza virus fusion occurs. This pH-based selection parameter identifies antibodies that remain stable and functional under virus infection conditions, improving neutralization efficacy.
2Measurement precision
If conventional antibody screening methods are used, then specific antibodies can be identified, but high-throughput screening capability is insufficient
Solution Approach 1:
The patent uses phage display technology to create copies of antibody variable regions on phage particles. Each phage displays an scFv on its surface while carrying the corresponding gene, enabling high-throughput screening where thousands of antibody variants can be displayed and tested simultaneously without requiring expression in host cells.
Solution Approach 2:
The patent achieves universality by designing a phage-displayed scFv library with universal display architecture where the same phage particle can present different scFv variants. This universal platform can be screened against multiple different viral antigens using the same methodology, greatly increasing screening productivity across different pathogen targets.
3Loss of time
If neutralizing antibodies are developed for immediate protection, then pandemic response time is reduced, but the complexity of identifying superior antibodies increases
Solution Approach 1:
The patent uses an intermediary acidic buffer solution (pH 5.0) as a mediator in the screening process. This buffer serves as a selective environment that automatically enriches for scFvs with neutralization capability without requiring complex multi-step assays or sophisticated instrumentation, simplifying the overall screening complexity while maintaining high throughput.
Data Source
AI summary
Disclosed herein are methods for high-throughput screening of a virus-specific neutralizing antibody. According to certain embodiments of the present disclosure, the virus is an influenza virus. Also disclosed herein are the antibodies selected by the high-throughput screening method, and the uses thereof in the prophylaxis and/or treatment of viral infection.