Multivalent Pneumococcal Conjugates Using Aprotic-Solvent Conjugation
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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 to certain serotypes, necessitating the development of vaccines that offer broader protection against a diverse range of pneumococcal strains.
Innovation Solution
Development of multivalent immunogenic compositions comprising Streptococcus pneumoniae polysaccharide-protein conjugates using CRM197 as a carrier protein, with specific serotypes conjugated in an aprotic solvent like DMSO to enhance stability and immunogenicity, and the use of these compositions in combination with complementary vaccines to induce a protective immune response.
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 pneumococcal polysaccharides with carrier proteins (such as tetanus toxoid or diphtheria toxin) to create a hybrid vaccine structure. This composite approach combines the T-independent antigen properties of polysaccharides with the T-dependent antigen properties of proteins, enabling effective immune response in infants while maintaining manufacturing feasibility.
Solution Approach 2:
The patent changes the chemical and immunological parameters of the polysaccharide vaccine by modifying its structure through conjugation with carrier proteins. This parameter change transforms the vaccine from a purely polysaccharide-based formulation to a conjugate vaccine, fundamentally altering its immunogenicity profile to work effectively in young children.
2Adaptability or versatility
If multivalent pneumococcal vaccines cover multiple serotypes, then broader protection is provided, but immune interference occurs between serotypes
Solution Approach 1:
The patent applies segmentation by dividing the multivalent vaccine into separate conjugate components, each targeting a specific serotype. This segmentation allows each serotype-specific polysaccharide-protein conjugate to function independently, minimizing immune interference while maintaining broad serotype coverage through combination vaccination.
Solution Approach 2:
The patent applies local quality by optimizing each individual polysaccharide-protein conjugate component with specific characteristics tailored to its target serotype. Each conjugate is locally optimized for maximum immunogenicity against its specific serotype, while the overall vaccine formulation maintains diversity across multiple serotypes.
3Device complexity
If polysaccharides are used as T-cell independent antigens, then the immune mechanism is simpler, but the antigens cannot be processed or presented on MHC molecules to interact with T-cells
Solution Approach 1:
The patent merges two distinct immune mechanisms by combining T-independent polysaccharide antigens with T-dependent protein carrier antigens in a single conjugate vaccine. This merging allows the vaccine to simultaneously engage both B-cell cross-linking (T-independent) and MHC-presented T-cell interaction (T-dependent) pathways, creating a synergistic immune response.
Solution Approach 2:
The patent uses the carrier protein as an intermediary that bridges the gap between polysaccharide antigens and T-cell recognition. The protein carrier acts as a mediator that can be processed and presented on MHC molecules to T-cells, while also carrying the polysaccharide antigen, thereby enabling T-cell dependent immune response to otherwise T-independent antigens.
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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 regimens that provide complementary protection for patients that have been vaccinated with a multivalent vaccine indicated for the prevention of pneumococcal disease.