Recombinant Salmonella Vaccine for Pneumococcal Serotype Coverage
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Solution Overview
Problem
Current vaccines against Streptococcus pneumoniae are limited in their ability to provide long-term protection, especially in developing countries, due to high costs and the rapid emergence of drug-resistant serotypes, and existing vaccines do not effectively immunize children under two years old or provide comprehensive coverage against the diverse serotypes of the pathogen.
Innovation Solution
A recombinant Salmonella bacterium capable of regulated expression of Streptococcus pneumoniae antigens and attenuation, with specific mutations that affect persistence and fluid secretion in hosts, is developed to elicit an immune response, comprising mutations such as ΔaroC1083, ΔaroD769, ΔPmurA25::TT araC PBAD murA, and Δpmi-2426, ΔPrfc174::TT araC PBAD rfc, and ΔsopB1925, which allows for controlled antigen production and immune response induction.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If capsule-based vaccines are used to protect against S. pneumoniae, then serotype-specific protection is achieved, but the vaccines are not immunogenic in children under two years old and do not cover all 90+ serotypes
Solution Approach 1:
The vaccine uses a universal carrier system (attenuated Salmonella) that can deliver multiple different pneumococcal antigens (from 90+ serotypes) through a single platform, making the vaccine applicable to diverse serotypes and potentially all age groups without needing separate vaccine formulations for each serotype or age group
Solution Approach 2:
The patent uses an intermediary carrier organism (attenuated Salmonella) to deliver pneumococcal antigens to the host immune system. This intermediary overcomes the limitations of direct polysaccharide vaccination by providing a biologically active delivery system that can stimulate immune responses in children under two years old and present multiple serotype antigens simultaneously
2Reliability
If conjugate vaccines are used to reduce carriage of vaccine types, then protection against invasive disease is improved, but non-vaccine serotypes occupy the vacated niche and cause replacement carriage
Solution Approach 1:
The vaccine platform can incorporate antigens from multiple serotypes (up to 90+) in a single formulation, preventing the need for selective pressure that leads to replacement carriage. By providing broad-spectrum coverage simultaneously, the vaccine eliminates ecological niches for non-vaccine serotypes
Solution Approach 2:
The vaccine provides preliminary protection against multiple serotypes before any single serotype can dominate. By pre-occupying immune resources and preventing colonization across diverse serotypes, the vaccine stops the replacement carriage phenomenon before it can occur
3Adaptability or versatility
If more capsular types are added to conjugate vaccines to cover diverse serotypes, then serotype coverage is improved, but the cost increases to US$260/course making it unaffordable for developing countries
Solution Approach 1:
The patent employs a universal delivery platform (attenuated Salmonella) that can accommodate multiple different pneumococcal antigens through genetic engineering. This single platform approach covers 90+ serotypes without requiring separate vaccine formulations for each serotype combination, dramatically reducing manufacturing complexity and cost compared to traditional conjugate vaccines
Solution Approach 2:
The invention changes the fundamental parameter of vaccine delivery from chemical conjugation (protein-polysaccharide conjugates) to biological delivery (live attenuated bacterium). This parameter change enables a single vaccine formulation to provide broad serotype coverage at lower cost by utilizing the natural immunogenicity and delivery capabilities of the Salmonella carrier
4Reliability
If existing vaccines are used in developing countries, then some protection is achieved, but the high cost and limited serotype coverage result in suboptimal protection where most disease occurs
Solution Approach 1:
The vaccine uses a cost-effective platform technology (attenuated Salmonella) that can be produced at lower cost than conjugate vaccines. The system provides comprehensive protection suitable for developing countries by delivering multiple serotype antigens through a single, affordable formulation that addresses the majority of pneumococcal disease burden
Data Source
AI summary
The invention encompasses a recombinant bacterium capable of eliciting an immune response against Streptococcus pneumoniae, a vaccine comprising the bacterium, and methods of using the bacterium.