Optimized Antigenic Polypeptides for Broad RNA Virus Protection
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Solution Overview
Problem
Current vaccine technologies are inadequate for emerging and re-emerging RNA viruses, such as those causing viral hemorrhagic fevers and influenza, due to high mutation rates and limited breadth of protection, requiring new methods to induce broadly neutralizing immune responses.
Innovation Solution
A method involving a polypeptide library of optimized antigenic pathogen polypeptides, screened for binding by broadly neutralizing antigen-binding molecules, to identify lead candidates capable of inducing a broadly neutralizing immune response, utilizing nucleic acid sequences and pseudotyped virus particles for immunization and neutralization assays.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional vaccine strategies using isolated pathogen genes are used, then vaccines can be produced for stable pathogens, but they fail to provide broad protection against mutating RNA viruses
Solution Approach 1:
The patent creates a polypeptide library where each polypeptide is designed to recognize multiple viral strains simultaneously. By incorporating consensus sequences that are conserved across different RNA virus isolates, the vaccine candidates achieve universal recognition capability, allowing a single vaccine to provide broad protection against diverse and mutating viral strains rather than strain-specific protection
Solution Approach 2:
The patent systematically varies amino acid sequences in the polypeptide library based on consensus sequences derived from multiple viral isolates. By optimizing amino acid composition and sequence parameters to match conserved regions across different strains, the invention transforms the vaccine from strain-specific to broadly protective while maintaining immunogenicity
2Ease of manufacture
If vaccine antigens are selected based on availability of wild-type strains, then vaccine development is simplified, but the selection process becomes empirical and time-consuming
Solution Approach 1:
The patent performs preliminary computational analysis to identify consensus sequences and critical amino acid positions before experimental vaccine development. By pre-screening and selecting polypeptide sequences based on in silico predictions of cross-strain recognition, the invention eliminates the need for time-consuming trial-and-error testing of multiple wild-type strain-based candidates, accelerating vaccine development while maintaining scientific rigor
3Adaptability or versatility
If polypeptide sequences are optimized from multiple pathogen isolates, then broad neutralization capability is enhanced, but the complexity of identifying lead candidates increases
Solution Approach 1:
The patent replaces complex, resource-intensive in vivo neutralization assays with in silico prediction algorithms and in vitro binding assays. By using computational models to predict cross-strain neutralization capability and simplified binding assays to screen the polypeptide library, the invention reduces screening complexity while maintaining the ability to identify broadly neutralizing candidates from optimized sequences
Data Source
AI summary
Methods for identifying optimized antigenic pathogen polypeptides capable of inducing a broadly neutralizing immune response, and associated T-cell responses, to a pathogen are described, as well as nucleic acid sequences encoding such polypeptides. Methods for determining whether a broadly neutralizing immune response is induced in a subject following immunization with an optimized antigenic pathogen polypeptide, or a nucleic acid encoding the optimized pathogen polypeptide, are also described. Nucleic acid molecules, polypeptides, vectors, cells, fusion proteins, pharmaceutical compositions, and their use as vaccines against pathogens, especially against emerging or re-emerging pathogens (particularly RNA viruses), are also described.