Pneumococcal Polysaccharide-Protein Conjugates for Broader Serotype Coverage
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Solution Overview
Problem
Current multivalent pneumococcal vaccines provide limited coverage against emerging pneumococcal serotypes and exhibit immune interference and lower response rates for certain serotypes, necessitating the development of compositions that offer broader protection against a diverse range of Streptococcus pneumoniae strains.
Innovation Solution
Development of multivalent immunogenic compositions comprising polysaccharide-protein conjugates from specific Streptococcus pneumoniae serotypes, including 15A, 16F, 23A, 23B, 24F, 31, and 35B, conjugated to a carrier protein, with the conjugation process utilizing an aprotic solvent like DMSO to enhance stability and immunogenicity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of manufacture
If unconjugated pneumococcal polysaccharides are used in vaccines, then the vaccine can be manufactured with simpler processes, but infants and young children respond poorly to the vaccine
Solution Approach 1:
The patent applies composite materials by conjugating polysaccharides with carrier proteins (such as CRM197, tetanus toxoid, or diphtheria toxoid) to create polysaccharide-protein conjugate vaccines. This composite structure combines the T-cell independent antigen properties of polysaccharides with the T-cell dependent antigen properties of proteins, enabling infants and young children to mount effective immune responses while maintaining manufacturing feasibility
Solution Approach 2:
The patent changes the chemical and immunological parameters of the polysaccharide antigen by conjugating it to carrier proteins. This transformation converts the antigen from T-cell independent to T-cell dependent, fundamentally altering how the immune system processes and responds to the vaccine, thereby achieving reliable immune responses in infants and young children
2Adaptability or versatility
If multivalent pneumococcal vaccines cover multiple serotypes, then broader protection is provided, but immune interference occurs reducing protection for certain serotypes
Solution Approach 1:
The patent segments the multivalent vaccine into separate polysaccharide-protein conjugate components for each serotype (e.g., serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, 23F). Each serotype-specific polysaccharide is independently conjugated to a carrier protein, allowing individual optimization of each component to minimize immune interference while maintaining broad serotype coverage
Solution Approach 2:
The patent applies local quality by optimizing each serotype-specific polysaccharide-protein conjugate component with appropriate carrier proteins and conjugation conditions. This allows tailoring the immunogenicity and stability of each serotype component to ensure reliable protection for specific serotypes while maintaining overall multivalent coverage
3Reliability
If polysaccharides are conjugated to carrier proteins to enhance immunogenicity in infants, then immune response improves, but the manufacturing process becomes more complex
Solution Approach 1:
The patent uses carrier proteins (CRM197, tetanus toxoid, or diphtheria toxoid) as intermediaries to bridge the polysaccharide antigen and the infant immune system. These carrier proteins serve as mediators that enable T-cell dependent immune responses to polysaccharide antigens, achieving enhanced immunogenicity in infants while providing a standardized platform for conjugation that manages manufacturing complexity
Data Source
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AI summary
The invention is related to multivalent immunogenic compositions comprising more than one S. pneumoniae polysaccharide protein conjugates, wherein each of the conjugates comprises a polysaccharide from an S. pneumoniae serotype conjugated to a carrier protein, wherein the serotypes of S. pneumoniae are as defined herein. In some embodiments, at least one of the polysaccharide protein conjugates is formed by a conjugation reaction comprising an aprotic solvent. In further embodiments, each of the polysaccharide protein conjugates is formed by a conjugation reaction comprising an aprotic solvent. Also provided are methods for inducing a protective immune response in a human patient comprising administering the multivalent immunogenic compositions of the invention to the patient. The multivalent immunogenic compositions are useful for providing protection against S. pneumoniae infection and diseases caused by S. pneumoniae. The compositions of the invention are also useful as part of treatment regimes that provide complementary protection for patieints that have been vaccinated with a multivalent vaccine indicated for the prevention of pneumococcal disease.