Serotype 6A Conjugate Vaccine Sizing for Immunogenicity and Filterability
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Solution Overview
Problem
Existing Streptococcus pneumoniae vaccines, particularly those targeting serotype 6A, face challenges in achieving high immunogenicity and filterability, limiting their effectiveness in preventing infections.
Innovation Solution
The development of sized Streptococcus pneumoniae serotype 6A polysaccharides, specifically sized to have an average molecular weight between 1000, 110-750, 150-500, 180-600, 210-490, 210-450, 180-400, 210-400, 210-370, 220-360, 230-350, 240-340, 240-320, 240-310, or 250-310 kDa, which are then conjugated to carrier proteins like CRM197, DT, or TT, enhancing their immunogenicity and filterability.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If native polysaccharides are used for vaccine conjugation, then immunogenicity may be sufficient, but filterability and manufacturing efficiency are poor
Solution Approach 1:
The patent applies parameter changes by controlling the molecular weight of polysaccharides through specific purification steps and sizing techniques. Polysaccharides are sized to specific molecular weight ranges (e.g., 100-1000, 110-750, 150-500, 180-600, 210-490, 210-450, 180-400, 210-400, 210-370, 220-360, 230-350, 240-340, 240-320, 240-310 or 250-310 kDa) to optimize both immunogenicity and filterability for vaccine manufacturing
Solution Approach 2:
The patent segments the polysaccharide population by molecular weight through purification and sizing processes. This creates distinct size fractions that can be selectively used for conjugation, improving both the immunogenicity of the vaccine and the ease of manufacturing by enhancing filterability
2Productivity
If polysaccharide size is reduced for better filterability, then manufacturing efficiency improves, but immunogenicity may decrease
Solution Approach 1:
The patent optimizes the molecular weight parameter of polysaccharides to specific ranges that balance filterability and immunogenicity. By controlling polysaccharide size to specific kDa ranges through purification and sizing, the invention achieves both improved manufacturing efficiency and maintained immunogenicity
Solution Approach 2:
The patent creates optimized copies of native polysaccharides with controlled molecular weights. These sized polysaccharide copies retain the immunogenic properties of native polysaccharides while possessing improved physical characteristics for manufacturing, including better filterability
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 sized and conjugated polysaccharides demonstrate improved immunogenicity and filterability, providing enhanced protection against Streptococcus pneumoniae infections, particularly in reducing the severity and frequency of exacerbations of chronic obstructive pulmonary disease (COPD).
Implementation Method 1
using mechanical and chemical sizing techniques such as high pressure homogenization
Implementation Method 2
using mechanical and chemical sizing techniques such as high pressure homogenization and periodate treatment
Implementation Method 3
conjugated to carrier proteins like CRM197, to enhance immunogenicity
Data Source
AI summary
The present invention is in the field of pneumococcal capsular saccharide conjugate vaccines. Specifically, the present invention relates to sized Streptococcus pneumoniae serotype 6A capsular polysaccharides, in particular Streptococcus pneumoniae serotype 6A capsular polysaccharides having the average size (e.g. Mw) of the Streptococcus pneumoniae serotype 6A capsular polysaccharide is between 100-1000 kDa, suitably conjugated to a carrier protein.


