Streptococcus pneumoniae Polysaccharide-Protein Conjugates in DMSO
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Solution Overview
Problem
Current polysaccharide vaccines for Streptococcus pneumoniae are ineffective in children under 2 years old due to the polysaccharides being T-cell independent antigens, which lack immunogenicity.
Innovation Solution
Conjugating polysaccharides from multiple S. pneumoniae serotypes to a carrier protein, such as CRM197, using reductive amination in an aprotic solvent like DMSO, to enhance immunogenicity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Device complexity
If polysaccharides are used as T-cell independent antigens, then the vaccine structure is simple, but the immunogenicity is poor especially in children under 2 years old
Solution Approach 1:
The patent combines polysaccharide antigens with protein carriers to create composite conjugate vaccines. This composite structure allows the polysaccharide component to maintain its simplicity while the protein carrier provides T-cell dependency, thereby enhancing immunogenicity in young children without significantly complicating the overall vaccine structure.
Solution Approach 2:
The patent merges T-cell independent polysaccharide antigens with T-cell dependent protein carriers into a single conjugate vaccine formulation. This merging allows the polysaccharide to benefit from the immunogenic enhancement provided by the protein carrier, enabling effective immune response in children under 2 years old while maintaining the structural advantages of polysaccharide-based vaccines.
2Reliability
If polysaccharides are conjugated to protein carriers, then the immunogenicity is enhanced, but the manufacturing process becomes more complex
Solution Approach 1:
The patent employs parameter changes in the conjugation process, specifically using dimethyl sulfoxide (DMSO) as a solvent instead of traditional aqueous buffers. This parameter change in the reaction medium optimizes the conjugation efficiency and immunogenicity of the polysaccharide-protein conjugates, while the standardized DMSO-based protocol actually simplifies the manufacturing process by reducing the need for extensive purification steps.
Solution Approach 2:
The patent substitutes traditional mechanical mixing and aqueous-based conjugation methods with a chemically optimized DMSO-based reductive amination process. This substitution replaces complex mechanical manipulation with a more controlled chemical reaction system that proceeds efficiently in DMSO, thereby enhancing immunogenicity while streamlining the manufacturing process.
3Ease of manufacture
If reductive amination is performed in aqueous solvent, then the process is simple, but the immunogenicity of the conjugates is reduced
Solution Approach 1:
The patent applies parameter changes by switching the solvent from aqueous to dimethyl sulfoxide (DMSO) in the reductive amination process. This parameter change fundamentally alters the reaction environment to enhance the immunogenicity of the resulting polysaccharide-protein conjugates. The DMSO-based process maintains operational simplicity while dramatically improving the immunogenic quality of the conjugates compared to traditional aqueous methods.
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 conjugation process in DMSO solvent increases the immunogenicity of the polysaccharide-protein conjugates, leading to a stronger immune response compared to conjugates prepared in aqueous conditions.
Implementation Method 1
reductive amination, wherein the aldehyde or ketone group on one component of the reaction reacts with the amino or hydrazide group on the other component, and the C═N double bond formed is subsequently reduced to C—N single bond by a reducing agent
Data Source
AI summary
The present invention provides immunogenic compositions having one or more polysaccharide-protein conjugates in which one or more polysaccharides from Streptococcus pneumoniae bacterial capsules are conjugated to a carrier protein in an aprotic solvent such as dimethylsulfoxide (DMSO). The present invention also provides methods for providing an enhanced immune response to a pneumococcal polysaccharide protein conjugate vaccine comprising administering to a human subject an immunogenic composition comprising polysaccharide-protein conjugates prepared in DMSO conditions.