Pneumococcal Polysaccharide-Protein Conjugates for Infant Immunogenicity
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Solution Overview
Problem
Current multivalent pneumococcal conjugate vaccines do not provide cross-protection against emerging serotypes 23A and 23B of Streptococcus pneumoniae, highlighting a need for the identification and characterization of these serotypes for inclusion in future vaccines to enhance immunogenicity, especially in infants and young children who respond poorly to unconjugated polysaccharides.
Innovation Solution
Purified capsular polysaccharides from Streptococcus pneumoniae serotypes 23A and 23B, along with their polysaccharide-protein conjugates, are developed, characterized by specific repeating units and molecular weights, and activated for conjugation to carrier proteins like CRM197, to enhance immunogenicity and provide cross-protection.
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 these unconjugated polysaccharides due to their T-cell-independent nature
Solution Approach 1:
The patent applies composite materials by chemically conjugating pneumococcal polysaccharides (serotypes 23A and 23B) to carrier proteins such as CRM197 or diphtheria toxoid. This creates a polysaccharide-protein conjugate vaccine that combines the immunogenic properties of both components, transforming the T-cell-independent response into a T-cell-dependent response that is effective in infants and young children.
2Reliability
If existing multivalent pneumococcal conjugate vaccines (covering serotypes 4, 6B, 9V, 14, 18C, 19F, 23F) are used, then protection against these specific serotypes is achieved, but there is no cross-protection against emerging serotypes 23A and 23B
Solution Approach 1:
The patent applies segmentation by identifying and isolating the specific capsular polysaccharide structures of serotypes 23A and 23B as distinct antigenic components. The purified polysaccharides from these emerging serotypes are then conjugated to carrier proteins to create targeted vaccine components that address the specific gap in protection against these serotypes.
Solution Approach 2:
The patent applies universality by developing a conjugate vaccine platform that can incorporate multiple serotype-specific polysaccharides (including 23A and 23B) with a common carrier protein system. This multi-valent approach provides broad protection against multiple serotypes simultaneously, enhancing the vaccine's versatility against both covered and emerging serotypes.
3Reliability
If polysaccharides from serotypes 23A and 23B are conjugated to carrier proteins, then immunogenicity in infants is enhanced through T-cell-dependent response, but the vaccine formulation becomes more complex
Solution Approach 1:
The patent applies parameter changes by modifying the chemical structure of the polysaccharides through oxidation to introduce reactive groups (aldehydes) that can form covalent bonds with the carrier protein. This chemical modification enables stable conjugation and transforms the immunological properties from T-cell-independent to T-cell-dependent response.
Solution Approach 2:
The patent uses carrier proteins (CRM197, diphtheria toxoid) as intermediaries that bridge the polysaccharide antigen and the infant immune system. These carrier proteins provide T-cell epitopes that facilitate antigen presentation and activation of T-helper cells, which in turn enhance B-cell responses to the polysaccharide component.
Data Source
AI summary
The present invention provides capsular polysaccharides from Streptococcuspneumoniae serotypes identified using NMR The present invention further provides polysaccharide-protein conjugates in which capsular polysaccharides from one or more of these serotypes are conjugated to a carrier protein such as CRM197. Polysaccharide-protein conjugates from one or more of these serotypes may be included in multivalent pneumococcal conjugate vaccines having polysaccharides from multiple additional Streptococcuspneumoniae serotypes.