FimH RNA Vaccine Stabilization for Scalable UTI Prevention
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Solution Overview
Problem
Existing technologies face challenges in producing FimH antigen at commercial scale and maintaining its functional conformation for effective vaccines against urinary tract infections caused by uropathogenic Escherichia coli, due to its instability and high production burdens.
Innovation Solution
A coding RNA is developed that encodes an antigenic polypeptide derived from Escherichia coli FimH, optionally with modifications to stabilize its conformation and includes additional peptide elements like donor strand peptides and antigen clustering domains, administered via lipid nanoparticles for efficient immune response induction.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Stability of the object's composition
If FimH is produced as a complex with its chaperone FimC, then FimH stability is improved, but production complexity and burden increase significantly
Solution Approach 1:
The patent extracts only the essential stabilizing element (donor strand peptide) from the complex chaperone system, eliminating the need for full FimC chaperone production while maintaining FimH stability. This reduces production complexity by producing FimH as a simplified construct rather than a complex multi-protein assembly.
Solution Approach 2:
The patent uses a simplified copy or mimicry of the chaperone function through a small donor strand peptide that replicates the essential stabilizing interaction without requiring the full chaperone protein structure, thereby reducing production burden while preserving stability.
2Quantity of substance
If FimH is produced in sufficient amounts for commercial scale, then vaccine effectiveness is improved, but production challenges and costs increase
Solution Approach 1:
The patent segments the FimH production system into essential and non-essential components, focusing production resources on the core antigenic polypeptide with minimal stabilizing elements, thereby enabling scalable commercial production without the burden of producing full chaperone complexes.
Solution Approach 2:
The patent changes the production parameters by using a simplified FimH construct that can be produced in higher yields without the complicating factors of chaperone co-expression, enabling commercial-scale manufacturing with improved ease of manufacture.
3Stability of the object's composition
If FimH is stabilized using donor strand peptide, then FimH conformation stability is improved, but manufacturing complexity increases
Solution Approach 1:
The patent applies local quality by adding only the specific donor strand peptide region needed for stabilization rather than modifying the entire FimH structure or adding full chaperone proteins, thereby achieving conformational stability with minimal added complexity.
Solution Approach 2:
The patent creates an asymmetric solution where a small donor strand peptide (asymmetric in size and complexity) is added to the FimH construct to provide stabilization, rather than using a symmetric or balanced approach like full chaperone complexes, reducing overall manufacturing complexity.
Data Source
AI summary
The disclosure is directed to a coding RNA encoding an antigenic polypeptide which is selected or derived from Escherichia coli FimH. The present disclosure is also directed to compositions and vaccines comprising said coding RNA. Further, the disclosure concerns a kit, particularly a kit of parts comprising the coding RNA, or the composition, or the vaccine. The disclosure is also directed to methods of treating or preventing a disorder caused by E. coli.