Attenuated Salmonella Bacteria for Autoimmune Tolerance Induction
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Solution Overview
Problem
Current treatments for Type 1 diabetes (T1D) are limited, with no cure available and human clinical trials using autoantigens like proinsulin and GAD65 showing disappointing results, highlighting the need for more effective methods to inhibit autoimmunity and prevent β cell destruction.
Innovation Solution
Development of attenuated Salmonella bacteria carrying nucleic acids encoding autoantigens under the control of an SPI2 promoter, potentially combined with immunomodulators, for oral delivery to modulate the immune response and induce tolerance, thereby preventing autoimmune destruction of pancreatic cells.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If attenuated Salmonella bacteria are used to deliver autoantigens, then immune response modulation and tolerance induction are improved, but device complexity and manufacturing difficulty increase
Solution Approach 1:
The patent uses attenuated Salmonella bacteria as an intermediary vehicle to deliver autoantigens and immunomodulators to the immune system. The bacteria serve as a natural carrier that can present antigens to immune cells while co-delivering immunomodulatory molecules, thereby modulating the immune response more effectively than direct antigen administration alone
Solution Approach 2:
The bacterial vector is engineered to contain multiple genetic elements including autoantigen genes, immunomodulator genes, and regulatory sequences, creating a composite biological system that performs multiple functions simultaneously - antigen delivery, immune stimulation, and tolerance induction
2Reliability
If autoantigen vaccination is combined with cytokine administration, then synergistic immune effect is improved, but treatment complexity increases
Solution Approach 1:
The patent merges the functions of autoantigen delivery and cytokine administration into a single bacterial vector system. The Salmonella bacteria are engineered to co-express both the autoantigen and immunomodulatory cytokines, allowing simultaneous delivery of multiple therapeutic agents through one administration rather than separate treatments
Solution Approach 2:
The engineered Salmonella vector serves multiple functions: it acts as an antigen carrier, an immunostimulant, and a cytokine delivery vehicle all in one system. This multi-functional approach simplifies the overall treatment regimen while maintaining the synergistic effects of combination therapy
Data Source
AI summary
Provided herein are attenuated Salmonella bacteria for expressing autoantigen alone or in combination with an immunomodulatory, as well as methods of using these bacteria to treat various autoimmune disorders.