Stable C. difficile Vaccine via Phosphoether Bond
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Solution Overview
Problem
Current vaccines for Clostridioides difficile (C. difficile) are unstable, particularly in acidic or basic conditions, and require cold storage, making them costly and complex to produce and deliver, while a stable liquid vaccine is needed to address the increasing incidence of C. difficile infections.
Innovation Solution
A synthetic saccharide of general formula (I) is developed, which is hydrolysis-resistant and shelf-stable, allowing for its use in liquid formulations, and can be conjugated with an immunogenic carrier to enhance immunogenicity and stability, serving as a marker for detecting antibodies against C. difficile bacteria.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of operation
If the C. difficile PS-II saccharide is used in a liquid vaccine formulation, then the vaccine can be easily stored and transported, but the saccharide hydrolyzes in water due to the chemical lability of the (1→6) phosphodiester bond
Solution Approach 1:
The patent modifies the chemical structure of the PS-II saccharide by replacing the labile (1→6) phosphodiester bond with a stable (1→6) phosphoether bond. This parameter change in the chemical linkage maintains the immunogenicity of the saccharide while eliminating its susceptibility to hydrolysis in aqueous environments, enabling stable liquid vaccine formulations without requiring cold storage.
2Stability of the object's composition
If the vaccine is lyophilized as a solid formulation, then the saccharide stability is improved, but the production cost and delivery complexity increase due to cold chain requirements
Solution Approach 1:
The patent changes the chemical parameter of the phosphodiester bond to a phosphoether bond, which fundamentally alters the stability profile of the saccharide. This modification allows the vaccine to be formulated as a stable liquid preparation that does not require lyophilization or cold chain storage, thereby reducing delivery complexity and production costs while maintaining saccharide stability.
3Stability of the object's composition
If the (1→6) phosphodiester bond is present in the PS-II saccharide, then the saccharide structure is maintained, but the bond cleaves in the presence of acids, bases or metal ions leading to degradation
Solution Approach 1:
The patent performs a chemical modification of the phosphodiester linkage to create a phosphoether bond. This parameter change in the chemical structure renders the saccharide resistant to cleavage by acids, bases, and metal ions, while preserving the essential structural features and immunogenicity of the original PS-II saccharide.
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 synthetic saccharide elicits protective immune responses, confers stability in acidic and basic conditions, and enables the creation of a shelf-stable liquid vaccine that can be stored at ambient temperatures, providing effective prevention and treatment against C. difficile infections.
Implementation Method 1
The C. difficile PS-II saccharide hydrolyzes in water due to the chemical lability of the (1→6) phosphodiester bond interconnecting the PS-II repeating units
Implementation Method 2
when covalently connected to a carrier protein, oligosaccharide antigens can elicit long lasting, T-cell-dependent protection
Data Source
AI summary
The present invention relates to a synthetic saccharide of general formulate (I) that is related to Clostridium difficile PS-II cell-surface polysaccharide and conjugate thereof. Said synthetic saccharide, said conjugate and pharmaceutical composition containing said synthetic saccharide or said conjugate are useful for prevention and/or treatment of diseases associated with Clostridium difficile. Furthermore, the synthetic saccharide of general formula (I) is useful as marker in immunological assays for detection of antibodies against Clostridium difficile bacteria.