Topical Pathogen Assay for Cellular Immunity Measurement
Solution Overview
Problem
Current cellular immunity assays are cumbersome and biased, failing to distinguish tissue-resident fighter T cells from nonfighter T cells, leading to inconsistencies and lack of comprehensive immunity measurement, particularly in gauging resistance to pathogens like SARS-CoV-2.
Innovation Solution
A novel method involving topical application of inactivated pathogen particles or tumor cells to the skin, recruiting immune cells and imaging structural changes to assess cellular immune response without contamination by nonfighter T cells, using techniques like raster-scanning optoacoustic mesoscopy for noninvasive imaging.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If conventional cellular immunity assays are used (PBMC stimulation with whole pathogens or antigen-specific assays), then immune response can be measured, but the assays are cumbersome and biased by nonfighter T cells
Solution Approach 1:
The invention segments the immune cell population by spatial location, separating tissue-resident fighter T cells (localized at the application site) from circulating nonfighter T cells (in peripheral blood). This segmentation is achieved by applying pathogen particles topically to skin and imaging only the localized immune response at the application site, thereby excluding nonfighter T cells from the measurement and improving measurement precision while simplifying the assay procedure.
2Measurement precision
If antibody-based humoral immunity assays are used, then serum antibody titers can be measured, but they are not well correlated with protective immunity
Solution Approach 1:
The invention uses tissue-resident fighter T cells as an intermediary marker that directly correlates with protective immunity. Instead of measuring serum antibodies (humoral immunity) which do not correlate well with protection, the assay measures the cellular immune response of tissue-resident T cells that are directly involved in protecting against pathogens at the tissue level, thereby improving correlation with protective immunity while providing a comprehensive assessment of cellular immunity.
3Ease of operation
If topical application of pathogen particles is used, then tissue-resident immune cells can be recruited and imaged, but the method requires new imaging techniques
Solution Approach 1:
The invention replaces complex surgical procedures and invasive tissue sampling with noninvasive optical imaging techniques. By using topical application of pathogen particles followed by optical imaging of the skin surface, the assay eliminates the need for surgery while achieving the same goal of measuring tissue-resident T cell response, thereby improving ease of operation. The imaging equipment complexity is offset by the elimination of surgical infrastructure requirements.
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 allows for an impartial, quantitative, and personalized assessment of cellular immune response, recruiting tissue-resident immune cells to the skin's surface, providing a comprehensive measure of protective immunity against various pathogens without surgical procedures, and synergizing with conventional antibody assays.
Implementation Method 1
topically applying pathogen particles or tumor cells to a site on an outermost layer of skin, wherein the pathogen particles or tumor cells can recruit immune cells to a site of administration
Implementation Method 2
imaging changes in cutaneous architecture driven by infiltration of immune cells at the site after at least one day from the applying step
Data Source
AI summary
Provided herein are methods of measuring a cellular immune response comprising: topically applying pathogen particles or tumor cells to a site on an outermost layer of skin, wherein the pathogen particles or tumor cells can recruit immune cells to the administration site; imaging the changes in cutaneous architecture driven by infiltration of immune cells at the site of administration after at least one day from the applying step; and characterizing one or more structural changes to one or more cutaneous layers at the site administration using an imager.