Antigen Processing Inhibition for Targeted Immune Response
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Solution Overview
Problem
Current methods lack effective vaccines for infections caused by viruses like cytomegalovirus (CMV), Epstein-Barr virus (EBV), and herpes simplex viruses (HSV), and existing treatments for HIV do not fully address the underlying causes of premature aging and comorbidities, leading to unmet clinical needs in managing infectious diseases.
Innovation Solution
The development of methods to alter the immune system by administering immune-modulating agents that inhibit or downregulate mediators of antigen processing, such as TAP and ERAAP, to induce antigen formation and stimulate an immune response against pathogen-encoded antigens in infected cells, using oligonucleotide molecules like siRNA or CRISPR proteins targeted to specific cells, including dendritic cells.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional vaccine methods are used, then immune response against pathogens is stimulated, but effective vaccines for CMV, EBV, HSV, and HIV have not been approved due to insufficient efficacy
Solution Approach 1:
Instead of directly vaccinating against pathogen antigens, the invention inverts the approach by downregulating TAP to induce novel antigen formation in infected cells, which then becomes the target for immune response. This indirect approach overcomes the failure of conventional direct vaccination methods.
Solution Approach 2:
The invention changes the parameter of antigen presentation by modulating TAP expression levels. By downregulating TAP, the system transforms the antigen landscape to present novel peptides that elicit effective immune responses against pathogens that have evaded conventional vaccines.
2Reliability
If TAP is downregulated to induce antigen formation, then immune response against pathogen-encoded antigens is enhanced, but antigen processing is inhibited
Solution Approach 1:
The invention converts the harmful effect of TAP downregulation (inhibited antigen processing) into a beneficial outcome by inducing novel antigen formation. The disruption of normal antigen processing pathways creates new antigenic targets that are highly immunogenic against infected cells.
3Reliability
If immune-modulating agents are administered to stimulate immune response, then severity or duration of infection is reduced, but complexity of treatment increases
Solution Approach 1:
The invention employs oligonucleotide molecules (siRNA, antisense RNA) that can autonomously target and downregulate TAP in infected cells. The treatment system essentially self-regulates by using nucleic acid-based agents that specifically recognize and silence the TAP gene in pathogen-infected cells, reducing treatment complexity.
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
These methods effectively direct the immune response to pathogen-encoded antigens, reducing the severity or duration of infections by eliciting a targeted anti-pathogenic immune response, particularly in cases of CMV, EBV, HSV, and HIV, without triggering autoimmune reactions.
Implementation Method 1
the immune-modulating agent comprises an oligonucleotide molecule, such as a small interfering RNA, or a micro RNA, or an antisense RNA directed against the mediator of antigen processing
Data Source
AI summary
The present invention relates, in part, to methods of generating immune responses in subjects to treat an infectious disease.