LFn Antigen Delivery Cytosol Transport Vaccine Adjuvant
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Solution Overview
Problem
Current vaccines face challenges in eliciting effective immune responses due to poor immunogenicity, particularly in delivering antigens to the cytosol for cell-mediated immune responses, and existing adjuvants can cause inflammation and hypersensitivity reactions, limiting their suitability for human vaccination.
Innovation Solution
The use of LF polypeptides, such as LFn, to deliver target antigens to the cytosol without being covalently linked, facilitating cell-mediated immune responses and acting as an adjuvant to enhance immune efficacy without the need for protective antigen (PA) of Bacillus anthracis.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional vaccines are used to stimulate immune response, then immunity is provided against pathogens, but poor immunogenicity limits effectiveness particularly in delivering antigens to cytosol for cell-mediated immune responses
Solution Approach 1:
The patent uses a bacterial toxin-derived delivery system as an intermediary to transport antigenic material into the cytosol. The toxin acts as a molecular vehicle that facilitates entry of the antigen through the cell membrane and into the cytosol, enabling cell-mediated immune responses that conventional vaccines cannot achieve effectively.
2Productivity
If bacterial toxins are used to deliver peptide epitopes to cell cytosol, then cell-mediated immune response is stimulated, but capacity to deliver larger protein antigens is limited and many individuals are already immunized against the carrier toxin
Solution Approach 1:
The patent segments the delivery system into a carrier toxin component and the antigenic material component. This segmentation allows the toxin to provide the delivery mechanism while the antigen can be independently selected and optimized, enabling the system to handle larger protein antigens and avoid pre-existing immunity issues by separating the carrier from the target antigen.
3Reliability
If adjuvants are used to enhance immune response, then effectiveness of vaccines is increased, but adjuvants can cause inflammation and hypersensitivity reactions limiting suitability for human vaccination
Solution Approach 1:
The patent converts the potentially harmful bacterial toxin into a beneficial delivery vehicle. By using the toxin's natural ability to penetrate cell membranes and deliver cargo, the system achieves effective intracellular antigen delivery without requiring separate adjuvants that would cause inflammation and hypersensitivity reactions.
4Adaptability or versatility
If whole protein antigens are used instead of peptides, then better vaccine suitability is achieved for broad application, but inability to enter cytosol and MHC pathway prevents stimulation of cell-mediated immune response
Solution Approach 1:
The patent employs the bacterial toxin as an intermediary delivery system that bridges the gap between whole protein antigens and the cytosol. The toxin binds to the whole protein antigen and facilitates its entry into the cytosol through the cell membrane, enabling MHC pathway processing and cell-mediated immune response while maintaining the advantages of using whole protein antigens.
Data Source
AI summary
The present invention is directed to a method for promoting or stimulating a cell-mediated immune response to an antigen, by administering a target antigen (such as a protein) with a transport factor that contains a fragment of a bipartite protein exotoxin, but not the corresponding protective antigen. Preferred transport factors include the protective antigen binding domain of lethal factor (LFn) from B. anthracis, consisting of amino acids 1-255, preferably a fragment of at least 80 amino acids that shows at least 80% homology to LFn, and a fragment of about 105 amino acids from the carboxy portion that does not bind PA. The target antigen can include any molecule for which it would be desirable to elicit a CMI response, including viral antigens and tumor antigens.