Pneumococcal Conjugate Composition for Broad Serotype Immunogenicity
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Solution Overview
Problem
Current pneumococcal vaccines have limited serotype coverage, particularly for Streptococcus pneumoniae serotypes 3 and 8, and are poorly immunogenic in children and elderly individuals, leading to inadequate protection against pneumococcal diseases.
Innovation Solution
Development of an immunogenic composition comprising a conjugate of saccharides from Streptococcus pneumoniae serotype 8 and a carrier protein, combined with a mixture of capsular polysaccharides from multiple serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F) individually conjugated to CRM 197 or protein D/tetanus/diphtheria toxoids, enhancing immune response and coverage.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Adaptability or versatility
If polysaccharide-based vaccines are used, then serotype coverage can be extended, but immunogenicity deteriorates in children and the elderly
Solution Approach 1:
The patent combines polysaccharide antigens from multiple serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, 23F) with carrier proteins (CRM197, protein D, tetanus toxoid, diphtheria toxoid) to create a conjugate vaccine. This composite structure provides both broad serotype coverage and enhanced immunogenicity through T-cell dependent antigen characteristics, resolving the contradiction between coverage and immunogenicity in vulnerable populations
Solution Approach 2:
The patent modifies the chemical and structural parameters of the vaccine components by using specifically sized polysaccharides (average molecular weight 38-158 kDa depending on serotype) and controlled conjugation ratios (e.g., 1:1 to 1:5 polysaccharide-to-protein ratios). These parameter changes optimize both the breadth of serotype coverage and the strength of immune response in children and the elderly
2Reliability
If conjugate vaccines are used to enhance immunogenicity, then immune response improves, but serotype coverage remains limited
Solution Approach 1:
The patent merges 14 different polysaccharide antigens from distinct pneumococcal serotypes into a single conjugate vaccine formulation, each conjugated to appropriate carrier proteins. This combination approach maintains the T-cell dependent immunogenicity benefits of conjugate vaccines while expanding protection to cover 85-90% of epidemiologically important serotypes
Solution Approach 2:
The vaccine employs multiple carrier proteins (CRM197, protein D, tetanus toxoid, diphtheria toxoid) that can each independently elicit strong immune responses, providing universal immunogenicity across different serotype components. This multi-functional carrier system ensures robust immunogenicity while accommodating the diverse polysaccharide antigens from 14 serotypes
3Adaptability or versatility
If serotype 3 polysaccharide is included in conjugate vaccine, then serotype coverage improves, but immune response efficiency deteriorates
Solution Approach 1:
The patent optimizes the polysaccharide size parameter for serotype 3 by controlling the average molecular weight to 38-158 kDa through specific purification and fractionation methods. This parameter optimization, combined with conjugation to CRM197 carrier protein at controlled ratios, significantly improves the immune response efficiency to serotype 3 polysaccharide, addressing the historically low responder rate of 63.5%
Data Source
Figure 1A~1D
Figure 1E~1G
Figure 2A
AI summary
The present invention relates to immunogenic compositions comprising a conjugate of a saccharide from Streptococcus pneumoniae serotype 8 and a carrier protein, and a mixture consisting of capsular polysaccharides from Streptococcus pneumoniae serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F individually conjugated to CRM197 carrier protein, or a mixture consisting of capsular polysaccharides from Streptococcus pneumoniae serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F individually conjugated to a carrier protein, wherein the capsular polysaccharides from Streptococcus pneumoniae serotypes 1, 4, 5, 6B, 7F, 9V, 14, and 23F are individually conjugated to protein D, the capsular polysaccharide from Streptococcus pneumoniae serotype 18C is conjugated to tetanus toxoid and the capsular polysaccharide from Streptococcus pneumoniae serotype 19F is conjugated to diphtheria toxoid. Said compositions are useful for the prevention and/or treatment of diseases caused by Streptococcus pneumoniae.