Anucleate Cell-Derived Vesicles for Antigen Loading
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Solution Overview
Problem
Current methods for triggering an in vivo antigen-specific immune response using red blood cells as carriers face challenges due to their irregular shape and transcriptional inactivity, limiting the effectiveness of standard transfection techniques and requiring chemically modified antigens and limited surface area for loading.
Innovation Solution
Passing a cell suspension of anucleate cells through a cell-deforming constriction to form anucleate cell-derived vesicles, which are then incubated with antigens or adjuvants, allowing them to enter the vesicles and be administered to stimulate an immune response.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If red blood cells are used as carriers for antigen delivery, then the immune response can be triggered, but the irregular shape and limited surface area of red blood cells limit the loading capacity and effectiveness of antigenic material
Solution Approach 1:
The red blood cell is segmented into multiple smaller vesicles through mechanical disruption methods (microfluidization, sonication, extrusion). This segmentation increases the total surface area available for antigen loading while maintaining the beneficial properties of red blood cell-derived membranes. The segmented vesicles can collectively carry more antigenic material than a single intact red blood cell.
Solution Approach 2:
The invention transitions from surface conjugation (2D loading) to internal encapsulation (3D loading). By creating vesicles with internal cavities, the system可以利用 both the membrane surface and the internal volume for antigen delivery, dramatically increasing the loading capacity beyond what is possible with surface attachment alone.
2Ease of manufacture
If standard transfection techniques are used to deliver antigen into red blood cells, then antigen delivery can be achieved, but the transcriptional inactivity and unique properties of red blood cells make standard techniques ineffective
Solution Approach 1:
The invention replaces biochemical transfection methods (which rely on cellular machinery like endocytosis or membrane fusion) with purely mechanical disruption methods. Techniques such as microfluidization, sonication, and extrusion physically break open the red blood cells to release vesicles containing antigen, bypassing the need for transcriptional or translational machinery that is absent in mature red blood cells.
Solution Approach 2:
The invention changes the physical state and structural parameters of red blood cells through controlled mechanical stress. By applying specific forces (shear stress in microfluidizers, ultrasonic vibrations, pressure differential in extruders), the cells are transformed from intact structures into vesicles with desired antigen-loading properties, creating a reliable delivery system adapted to red blood cell characteristics.
3Ease of operation
If chemically modified antigens are used for attachment to red blood cells, then antigen delivery can proceed, but the need for chemical modification increases complexity and may reduce antigen efficacy
Solution Approach 1:
The invention extracts the membrane from red blood cells to create vesicles, separating the beneficial membrane properties (recognition by immune system, biocompatibility) from the constraints of the intact cell structure. This extracted membrane forms vesicles that can be loaded with native, unmodified antigens through simple encapsulation during vesicle formation, eliminating the need for chemical conjugation procedures.
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 method enhances the delivery and immune response efficacy by overcoming the limitations of red blood cell shape and surface area constraints, enabling effective antigen and adjuvant loading and presentation, thereby stimulating a robust immune response.
Implementation Method 1
passing a cell suspension comprising an input anucleate cell through a cell-deforming constriction, wherein a diameter of the constriction is a function of a diameter of the input anucleate cell in the suspension, thereby causing perturbations of the input anucleate cell large enough for the antigen to pass through
Implementation Method 2
incubating the anucleate cell-derived vesicle with the antigen for a sufficient time to allow the antigen to enter the anucleate cell-derived vesicle
Data Source
AI summary
The present invention provides methods for stimulating an immune response to an antigen comprising administering to an individual, an anucleate cell-derived vesicle comprising an antigen and/or an adjuvant. In some embodiments, the anucleate cell-derived vesicle comprising the antigen and/or adjuvant is generated by passing a cell suspension containing an input anucleate cell through a constriction, wherein the constriction deforms the input anucleate cell thereby causing a perturbation of the cell to form an anucleate cell-derived vesicle such that an antigen and/or an adjuvant enters the anucleate cell-derived vesicle. In some embodiments, the anucleate cell-derived vesicle comprising the antigen and/or adjuvant is delivered to an individual and the antigen is delivered to and processed in an immunogenic environment to treat a disease, prevent a disease, and/or vaccinate an individual against an antigen.