Engineered Salmonella Typhi Vectors for OmpA/OmpW Outer-Membrane Antigens
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Solution Overview
Problem
There is a lack of effective vaccines against multidrug-resistant Acinetobacter baumannii and Klebsiella pneumoniae, which are causing nosocomial infections with high morbidity and mortality, and existing antibiotic treatments are limited by resistance and side effects.
Innovation Solution
Development of a live Salmonella enterica typhi vector vaccine engineered to express heterologous outer membrane proteins (OmpA and OmpW) from these pathogens, delivering them via recombinant outer membrane vesicles (rOMVs) to mucosal tissues for enhanced immune response.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional vaccines and antibiotic treatments are used against multidrug-resistant Acinetobacter baumannii and Klebsiella pneumoniae, then treatment options are limited, but morbidity and mortality remain high
Solution Approach 1:
The patent uses attenuated Salmonella typhi as a live vector intermediary to deliver heterologous outer membrane proteins (OmpA and OmpW) from A. baumannii and K. pneumoniae. This mediator approach allows the vaccine to present pathogen antigens in a safe, controlled manner, inducing robust mucosal and systemic immune responses without directly exposing patients to the deadly pathogens themselves
2Ease of manufacture
If antibiotics are used to treat multidrug-resistant infections, then some infections can be treated, but resistance and side effects limit treatment options
Solution Approach 1:
The patent extracts the protective antigens (OmpA and OmpW outer membrane proteins) from the problematic multidrug-resistant pathogens A. baumannii and K. pneumoniae and expresses them in a safe live vector system. This extraction allows the essential protective components to be separated from the harmful pathogenic elements, creating a vaccine that targets the pathogens without requiring antibiotics
3Reliability
If vaccines are developed to target outer membrane surface antigens, then protective efficacy can be achieved, but antigenic variation due to genome plasticity poses challenges
Solution Approach 1:
The patent targets highly conserved outer membrane proteins (OmpA and OmpW) that are essential for the survival and function of A. baumannii and K. pneumoniae. These universal antigens are present across diverse clinical isolates and are difficult to eliminate due to their critical roles in bacterial physiology, providing broad protective efficacy against antigenic variation
4Reliability
If live Salmonella typhi vectors are engineered to express heterologous antigens, then robust immune responses can be induced, but vaccine complexity increases
Solution Approach 1:
The patent employs a nested structure where heterologous antigen genes (OmpA and OmpW from A. baumannii and K. pneumoniae) are inserted into the genome of the attenuated Salmonella typhi live vector. This nested gene arrangement allows the complex immune-stimulating function to be achieved through a organized, modular genetic construction that integrates multiple antigens within a single safe carrier system
Data Source
AI summary
The present invention provides compositions and methods of inducing an immune response in a subject in need thereof, comprising administering to the subject an immunologically-effective amount of a live Salmonella typhi vector comprising a heterologous antigen from a pathogen, wherein the heterologous antigen comprises an outer membrane protein, an antigenic fragment thereof or a variant thereof, wherein the antigen is delivered to a mucosal tissue of the subject by an outer membrane vesicle.