Bacteria-derived vesicles and uses thereof
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Solution Overview
Problem
Existing bacterial vesicle vaccines activate innate immunity, causing severe side effects such as fever and flu-like symptoms, while still inducing protective immunity.
Innovation Solution
Development of non-naturally occurring artificial outer membrane vesicles (aOMVs) derived from gram-negative bacteria, depleted of certain components and enriched in outer membrane proteins, which are used in conjunction with tumor vesicles and immune checkpoint inhibitors to treat cancer, optionally loaded with therapeutic agents like STING agonists.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If naturally released bacterial vesicles (OMVs) are used as vaccines, then protective immunity is induced, but severe side effects occur due to activation of innate immunity
Solution Approach 1:
The patent extracts and removes harmful components (LPS, nucleic acids, cytoplasmic proteins, inner membrane proteins) from the bacterial vesicles while retaining the beneficial outer membrane proteins that induce protective immunity. This selective extraction resolves the contradiction by eliminating the source of harmful immune activation while preserving immunogenicity.
Solution Approach 2:
The patent creates vesicles with non-uniform composition where different regions and components have different functions. The outer membrane proteins are enriched to provide immunogenicity, while harmful components like LPS are depleted or removed. This local differentiation of quality allows the vesicle to simultaneously provide protection without causing severe side effects.
2Object-affected harmful factors
If bacterial vesicles are modified to reduce side effects by removing harmful components, then severe side effects are reduced, but immunogenicity may be compromised
Solution Approach 1:
The patent systematically changes the compositional parameters of the bacterial vesicles by controlling the depletion of harmful components (LPS, nucleic acids, cytoplasmic proteins) while simultaneously enriching for outer membrane proteins. This parameter optimization ensures that immunogenicity is maintained or enhanced while side effects are reduced.
Solution Approach 2:
The patent creates a composite vesicle structure combining purified outer membrane proteins with reduced harmful components. This composite approach allows the vesicle to function as both an immunogen and a safe vaccine platform, resolving the contradiction between maintaining immunogenicity and reducing side effects.
3Adaptability or versatility
If artificial outer membrane vesicles are engineered to be enriched in outer membrane proteins and depleted of harmful components, then the vesicles can be used for cancer treatment, but the manufacturing process becomes more complex
Solution Approach 1:
The patent segments the manufacturing process into distinct stages: generation of bacterial vesicles, purification of outer membrane proteins, depletion of harmful components, and formulation with cancer antigens. This segmentation makes the complex manufacturing process more manageable and scalable while achieving the desired product characteristics.
Solution Approach 2:
The patent performs preliminary actions during vesicle generation and purification to pre-establish the desired composition (enriched outer membrane proteins, depleted harmful components) before final formulation with cancer antigens. This preliminary preparation simplifies subsequent steps and ensures product quality consistency.
Data Source
AI summary
Non-naturally occurring vesicles derived from bacteria, e.g., pathogenic bacteria, methods for making the vesicles, and methods for using compositions of these vesicles are disclosed. Methods of using the vesicles include prevention and/or treatment of bacterial infections. Also provided herein are compositions that include vesicles derived front bacteria and tumor vesicles, methods for making the tumor vesicles, and methods for using the compositions of bacterial vesicles and tumor vesicles. Methods of using the compositions of bacterial vesicles and tumor vesicles include treatment of cancer in a subject. Tumor vesicles may be derived from cancer cells present in the subject to be treated or from a cancer cell line expressing at least one neoantigen. The neoantigen may be specific to the subject and may have been identified by sequencing of the cancer cells from the subject. The neoantigen may be a neoantigen known to be commonly expressed in a particular type of cancer.