RNA Adjuvants Modulating Interferon Response for Vaccine Efficacy
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Solution Overview
Problem
RNA vaccines are costly, require high doses of RNA, and have limited long-term efficacy for infectious disease prevention, along with causing unwanted side effects due to modulation by the interferon system and current vaccine compositions.
Innovation Solution
Compositions comprising nucleic acids encoding synthetic proteins with functional fragments of toll-like receptor (TLR) agonists, such as TLR5, TLR4, and TLR2, combined with delivery vehicles for intranasal, oral, or intramuscular administration, to induce an initial innate immune response and enhance vaccine efficacy.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If RNA vaccines use host cell machinery for translation, then protein production is achieved, but the interferon system modulates translation and reduces RNA efficacy
Solution Approach 1:
The patent introduces TLR agonists as intermediary molecules that modulate the host cell's interferon system. These agonists act as mediators between the RNA vaccine and the immune system, optimizing the translation process by reducing interferon-mediated suppression while maintaining protein production efficiency and enhancing vaccine efficacy.
2Reliability
If current vaccine compositions are used, then immune response is elicited, but unwanted side effects occur
Solution Approach 1:
The patent modifies the composition parameters by incorporating specific TLR agonists (TLR2, TLR4, or TLR5 agonists) at optimized concentrations and ratios with the RNA vaccine. This parameter optimization enhances immune response reliability while minimizing harmful side effects through controlled modulation of the interferon system and targeted activation of toll-like receptor pathways.
3Productivity
If high dose of RNA is used, then sufficient protein production is achieved, but vaccine cost increases
Solution Approach 1:
The patent changes the translational parameters by using TLR agonists to optimize host cell machinery efficiency. This allows achieving sufficient protein production with lower RNA doses, as the agonists enhance translation efficiency and reduce interferon-mediated suppression, thereby decreasing the quantity of RNA needed while maintaining productivity.
4Reliability
If RNA vaccines are administered, then initial immune response is elicited, but long-term efficacy is limited
Solution Approach 1:
The patent applies preliminary action by incorporating TLR agonists that pre-modulate the immune system's interferon response pathways before the RNA vaccine fully executes its protein production function. This preliminary modulation optimizes the initial immune response and sets up enhanced long-term efficacy by programming the immune system's response characteristics in advance.
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
The proposed compositions reduce the required RNA dose, minimize side effects, and promote both innate and adaptive immune responses, thereby enhancing the long-term efficacy of RNA vaccines.
Implementation Method 1
the synthetic protein comprises at least a functional fragment of a toll-like receptor 5 (TLR5) agonist that is capable of activating a TLR5 pathway in a cell upon contact with the cell
Data Source
AI summary
Provided herein are adjuvants, compositions, and methods for the prevention and treatment of infectious diseases and cancer. Various toll-like receptor (TLR) agonists and RNA encoding TLR agonists are provided herein. The adjuvants provided herein can be complexed with a carrier or formulated with a delivery vehicle for administration to a subject. Further provided are adjuvants that can be delivered with vaccine compositions or as part of a vaccine composition to enhance the innate immune response in a subject.