Segmented mRNA Vaccine Adjuvant and Antigen Delivery
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Solution Overview
Problem
Current immunostimulatory compositions face challenges in eliciting both innate and adaptive immune responses effectively due to inefficient translation of mRNA when complexed with polycationic compounds, which impede the release of mRNA for protein expression.
Innovation Solution
An immunostimulatory composition comprising an adjuvant component of mRNA complexed with a polycationic peptide or protein, where the mRNA encoding an antigen is administered separately to ensure efficient translation and immune response activation, with a molar ratio of adjuvant to mRNA ranging from 0.1:1 to 1:0.01, allowing for enhanced immune response without interference from the complex.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If mRNA is complexed with polycationic compounds to form adjuvant component, then immunostimulatory response is enhanced, but translation efficiency of mRNA decreases
Solution Approach 1:
The invention divides the immunostimulatory composition into two separate components: (a) an adjuvant component comprising mRNA complexed with polycationic compounds, and (b) free antigen-encoding mRNA. This segmentation allows each component to perform its specific function optimally - the complexed mRNA provides immunostimulation while the free mRNA ensures efficient translation, thereby resolving the contradiction between enhanced immune response and maintained translation efficiency.
2Stability of the object's composition
If mRNA is complexed with polycationic compounds, then stability of mRNA is improved, but release of mRNA for protein expression is impeded
Solution Approach 1:
By segmenting the composition into complexed mRNA (for stability) and free mRNA (for easy release and translation), the invention ensures that mRNA stability is improved through complexation while simultaneously ensuring that protein expression is not impeded by providing separate free mRNA molecules that can be readily translated.
Solution Approach 2:
The polycationic compounds act as intermediaries that stabilize the complexed mRNA component without interfering with the free mRNA component. These intermediaries provide the necessary stability to the adjuvant component while allowing the free mRNA to maintain its natural properties for efficient translation.
3Reliability
If adjuvant and antigen-encoding mRNA are administered together, then immune response activation is enhanced, but translation of antigen mRNA is interfered with
Solution Approach 1:
The invention segments the immunostimulatory agents into distinct components that can be administered together without interference. The adjuvant component (complexed mRNA) and antigen-encoding mRNA are separate entities that simultaneously enhance immune response activation while allowing uninterrupted translation of the antigen.
Solution Approach 2:
Different regions of the composition have different qualities - the adjuvant component is designed for immunostimulation with stable complexation, while the antigen-encoding mRNA region maintains free state for optimal translation. This local differentiation of properties allows both functions to operate at peak efficiency simultaneously.
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
This approach enables efficient elicitation of both innate and adaptive immune responses by stabilizing the mRNA complex and ensuring effective translation of the antigen-encoding mRNA, improving immune response efficacy while maintaining the adjuvant's immunostimulatory properties.
Implementation Method 1
an adjuvant component, comprising or consisting of at least one (m)RNA, complexed with a polycationic peptide or protein
Implementation Method 2
They recognize conserved molecular patterns that distinguish foreign organisms, like viruses, bacteria, fungi and parasites from cells of their hosts. Such pathogen-associated molecular patterns include viral nucleic acids
Implementation Method 3
Following ligand-binding they transduce the signal via cytoplasmic adaptor proteins which leads to triggering of a host-defence response and entailing production of antimicrobial peptides, proinflammatory chemokines and cytokines, antiviral cytokines, etc.
Data Source
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AI summary
The present invention relates to an immunostimulatory composition comprising a) an adjuvant component, comprising or consisting of at least one (m)RNA, complexed with a cationic or polycationic compound, and b) at least one free mRNA, encoding at least one therapeutically active protein, antigen, allergen and/or antibody, wherein the immunostimulatory composition is capable to elicit or enhance an innate and optionally an adaptive immune response in a mammal. The inventive immunostimulatory composition may be a pharmaceutical composition or a vaccine. The invention furthermore relates to a method of preparation of the inventive immunostimulatory composition. The invention also relates to the use of the inventive immunostimulatory composition or its components (for the preparation of a pharmaceutical composition or a vaccine) for the treatment of various diseases. Finally, the invention relates to kits containing the inventive immunostimulatory composition, its components and/or the pharmaceutical composition or vaccine.