Microparticles from streptococcus pneumoniae as vaccine antigens
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Solution Overview
Problem
Current pneumococcal vaccines are serotype-dependent, providing limited protection against non-vaccine types and are costly to produce, with challenges in eliciting effective opsonophagocytic antibodies.
Innovation Solution
Isolation and use of Streptococcus pneumoniae membrane vesicle microparticles (MPs) enriched with specific proteins (Ply, LytA, PspC, RrgB) and optionally capsular polysaccharides, which are administered with an adjuvant to induce serotype-independent immunological responses and opsonophagocytic antibodies.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If pneumococcal conjugate vaccines targeting limited capsular serotypes are used, then protection against vaccine-type infections is improved, but non-vaccine type pneumococci rapidly expand and replace vaccine-types
Solution Approach 1:
The vaccine is segmented into multiple components, each targeting different capsular serotypes. PCV13 contains 13 different polysaccharide antigens conjugated to carrier proteins, allowing simultaneous protection against multiple serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, 23F) while maintaining focused immunogenicity for each component
Solution Approach 2:
The vaccine employs universal mechanisms that transcend serotype specificity. Conjugation technology creates a universal platform where polysaccharide antigens from different serotypes are linked to common carrier proteins (tetanus toxoid, diphtheria toxoid, or CRM197), enabling broad-spectrum protection through a single vaccine formulation that addresses multiple serotypes simultaneously
2Adaptability or versatility
If multiple antigens covering various capsular serotypes are included in vaccines, then broad protection is improved, but production costs increase
Solution Approach 1:
Multiple polysaccharide antigens from different capsular serotypes are merged into a single conjugate vaccine formulation. The 13 different polysaccharide antigens are chemically conjugated to carrier proteins and formulated together in one vaccine dose, achieving broad serotype coverage while streamlining manufacturing into a single product rather than requiring multiple separate vaccines
Solution Approach 2:
The vaccine utilizes parameter changes in antigen presentation by converting pure polysaccharides into conjugate structures. The conjugation process modifies the physical and immunological parameters of the polysaccharide antigens, linking them to protein carriers, which enhances immunogenicity and enables broader protection without proportionally increasing production complexity
3Reliability
If serotype-specific vaccines are used, then protection against specific serotypes is improved, but serotype-independent immunological responses are limited
Solution Approach 1:
Carrier proteins serve as intermediaries that bridge the gap between serotype-specific polysaccharide antigens and the immune system's ability to generate broad protection. The carrier proteins (tetanus toxoid, diphtheria toxoid, or CRM197) mediate the conjugation process and facilitate T-cell dependent immune responses, enabling the vaccine to generate both serotype-specific and serotype-independent immunity
Solution Approach 2:
The vaccine employs composite material structure combining polysaccharide antigens with protein carriers. This composite conjugate structure integrates the serotype-specificity of polysaccharides with the high immunogenicity of proteins, creating a hybrid antigen that elicits both type-specific opsonophagocytic antibodies and broader serotype-independent immune responses
Data Source
AI summary
An isolated Streptococcus pneumoniae membrane vesicle microparticle (MP), wherein said MP comprises: the protein Ply at the level of ≥0.070 μg/mg total protein in the MP; and/or the protein LytA at the level of ≥0.070 μg/mg total protein in the MP; and/or the protein PspC at the level of ≥0.130 μg/mg total protein in the MP; and/or the protein RrgB at the level of ≥0.020 μg/mg total protein in the MP. Compositions comprising such MPs. Uses thereof in particular in immunization, as well as methods of manufacture thereof.