Multi-Antigen ETEC and Campylobacter Vaccine Construct
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Solution Overview
Problem
Current vaccines for enterotoxigenic Escherichia coli (ETEC) and Campylobacter jejuni are inadequate in providing broad and long-term protection due to challenges such as antigen diversity, immunogenicity issues, and the risk of inducing autoimmune responses like Guillain-Barre Syndrome, with no FDA-licensed vaccines available for either pathogen.
Innovation Solution
A multi-agent immunogenic construct comprising a Campylobacter jejuni capsule polysaccharide conjugated to an enterotoxigenic Escherichia coli recombinant polypeptide construct, where the ETEC recombinant polypeptide is formed by connecting fimbrial subunits via polypeptide linkers and donor strand complementation to stabilize and enhance immunogenicity, avoiding undesirable associations and proteolytic degradation.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Adaptability or versatility
If a single-pathogen vaccine is used for ETEC or C. jejuni, then the vaccine can target a specific pathogen, but it cannot provide protection against multiple pathogens causing bacterial diarrhea
Solution Approach 1:
The patent combines ETEC fimbrial antigens and C. jejuni capsule polysaccharide antigens into a single conjugate vaccine construct. The polysaccharide is conjugated to a protein carrier that contains ETEC fimbrial subunits, creating a multi-antigen vaccine that provides protection against both pathogens simultaneously, directly resolving the contradiction between pathogen coverage and vaccine complexity.
Solution Approach 2:
The vaccine construct serves multiple functions: the ETEC fimbrial antigens provide protection against ETEC, the C. jejuni capsule polysaccharide provides protection against C. jejuni, and the conjugate structure enhances immunogenicity of the polysaccharide component. This multi-functionality allows a single vaccine to address multiple pathogens and immunological requirements.
2Reliability
If C. jejuni lipooligosaccharide is used as vaccine antigen, then the vaccine can induce immune response against C. jejuni, but it may induce autoimmune responses like Guillain-Barre Syndrome
Solution Approach 1:
The patent extracts only the capsule polysaccharide portion from the complete C. jejuni lipooligosaccharide structure, deliberately excluding the lipid A and core oligosaccharide components that are responsible for molecular mimicry with human gangliosides. This extraction maintains the protective immunogenicity of the polysaccharide while removing the harmful autoimmune-inducing elements.
Solution Approach 2:
The patent converts the potentially harmful complete lipooligosaccharide into a beneficial vaccine component by using the polysaccharide portion alone. The polysaccharide capsule is a virulence factor of C. jejuni that normally protects the bacteria, but when used as a vaccine antigen without the lipid components, it induces protective immunity without triggering autoimmune responses, effectively converting a harmful structure into a safe and effective vaccine component.
3Reliability
If polysaccharide antigen is used alone, then the vaccine can provide protection against encapsulated bacteria, but it fails to provide T-cell dependent immunity and has poor immunogenicity
Solution Approach 1:
The patent creates a composite vaccine construct where the C. jejuni capsule polysaccharide is chemically conjugated to a protein carrier containing ETEC fimbrial subunits. This composite structure combines the T-independent immunogenicity of polysaccharide with the T-dependent immunogenicity of protein, generating a robust T-cell dependent immune response with high immunogenicity while maintaining protection against encapsulated bacteria.
4Reliability
If ETEC vaccines focus on LT toxin or CF antigens, then the vaccine can induce anti-LT immunity or anti-CF immunity, but it cannot achieve sufficiently broad and long-term protection due to antigen diversity
Solution Approach 1:
The patent segments the ETEC fimbrial structure into major and minor subunits and includes both types in the vaccine construct. The minor subunits (adhesins) are present at low stoichiometric ratios in native fimbriae but are overrepresented in the vaccine to enhance their immunogenicity. This segmentation and strategic inclusion of multiple subunit types addresses the antigen diversity challenge by targeting multiple epitopes within the fimbrial structure.
Solution Approach 2:
The patent applies local quality enhancement by specifically increasing the representation of minor fimbrial subunits (adhesins) in the vaccine construct relative to their natural abundance. This localized enhancement of specific subunit types ensures that the less immunogenic but functionally critical adhesin components are adequately represented to induce protective immunity, addressing the diversity coverage issue.
Data Source
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AI summary
The inventive subject matter relates to a construct comprising antigens derived from multiple enterobacteria including Campylobacter jejuni capsule polysaccharide polymer, enterotoxigenic Escherichia coli recombinant polypeptide construct and lipopolysaecharide from Shigella spp.. The subject invention also relates to a method of inducing an immune response utilizing the inventive composition.