Pneumococcal Conjugate Vaccine Stabilization with Polysorbate 20
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Solution Overview
Problem
Current pneumococcal vaccines, such as Prevnar 13 and 14-valent vaccines, have limitations in serotype coverage and emerging serotypes, and formulations with surfactants like polysorbate 80 can lead to polysaccharide-protein conjugate instability and aggregation.
Innovation Solution
A 15-valent pneumococcal conjugate vaccine formulation using polysorbate 20 and a pH buffered saline solution with specific surfactant systems, including poloxamer and polyols, to stabilize polysaccharide-protein conjugates prepared in aqueous and aprotic solvents like DMSO, with aluminum phosphate adjuvant and CRM 197 carrier protein.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If polysorbate 80 is used as a surfactant in pneumococcal conjugate vaccine formulations, then the formulation can provide surfactant protection, but polysaccharide-protein conjugate instability and aggregation occur
Solution Approach 1:
The patent changes the surfactant parameter from polysorbate 80 to polysorbate 20, which has different molecular properties (different hydrophilic-lipophilic balance and chain structure). This parameter change resolves the contradiction by providing surfactant protection without inducing conjugate aggregation and instability, as demonstrated by the improved stability data in the patent.
2Ease of manufacture
If unconjugated pneumococcal polysaccharides are used, then the vaccine can be simpler to manufacture, but infants and young children respond poorly to the immunogen
Solution Approach 1:
The patent uses composite material construction by chemically conjugating pneumococcal polysaccharide immunogen to a carrier protein (such as tetanus toxoid or diphtheria toxoid). This creates a polysaccharide-protein conjugate that combines the immunogenic properties of both components, enabling T-cell dependent immune responses in infants while maintaining manufacturability.
3Adaptability or versatility
If serotype coverage is expanded to address emerging serotypes, then the vaccine provides broader protection, but the formulation complexity and manufacturing difficulty increase
Solution Approach 1:
The patent employs a universal carrier protein (such as CRM197 or other toxoids) that can serve multiple functions across different serotypes. This single carrier protein system can be conjugated to various pneumococcal polysaccharides from different serotypes, providing broad serotype coverage without requiring separate carrier systems for each serotype, thereby reducing formulation and manufacturing complexity.
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 formulation enhances stability and immunogenicity, reducing serotype-specific immune responses and addressing emerging serotypes, with improved particle size distribution and immunogenicity in animal models.
Implementation Method 1
The present invention provides pneumococcal conjugate vaccine formulations comprising surfactant systems incorporating polysorbate 20
Data Source
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AI summary
The present invention provides pneumococcal conjugate vaccine formulations comprising surfactant systems incorporating polysorbate 20 or a combination of a poloxamer and a polyol.