# Advancing immune organoid technology and organoid combinations > **NIH NIH U19** · STANFORD UNIVERSITY · 2024 · $553,826 ## Abstract PROJECT SUMMARY In this technology development project, we want to continue the significant progress that we made in this last granting period and take advantage of the many opportunities that we see to make human immune organoids an indispensable system for understanding human immune responses to vaccination and infection. Fortunately, we have made several major advances in our organoid work recently, especially our focus on spleen organoids that we obtain through our collaboration with Donor Network West, which now regularly supplies us with both spleens, skin, blood and lung fragments from a given donor. We have found that spleens are much more diverse in cell types than tonsils and are easier to get responses from both RNA vaccines and novel ones(to most individuals) such as Yellow Fever Vaccine. We will use them in Aim 1. to optimize the protocols for flu and SARS- CoV-2 RNA vaccines, and specifically to determine how well organoid responses compare with available studies in live humans, using our available reagents for T and B cell responses. An even deeper exploration of the BCR and TCR repertoire will be achieved by sequence analysis, which the Boyd and Davis groups are very experienced at. In Aim 2 we will focus on getting complete T and B cell responses with the Yellow Fever vaccine, currently producing only IgM antibodies. In Aim 3, we will take advantage of promising results we have obtained showing that a highly multimerized peptide-MHC reagent (60-mer) can stain specific T cells in fixed sections, as can a reagent for specific B cells. These would be a very valuable reagents to interrogate specific lymphocytes in the most standard type of clinical specimen. In Aim 4, we are teaming up with Drs. Kuo and Blish to use lung and spleen organoids from the same donors to see any form of cooperativity when we infect the lungs with influenza or SARS-CoV-2. Since we can see infiltration and rejection with co-incubated skin and tonsils/spleen from unmatched donors, we are confident that there will cooperativity, as we expect antigen loaded dendritic cells will migrate from infected lungs and trigger a response in nearby spleen organoids. Lastly, in Aim 5 we suspect that there are distinct differences in the immune responses of inbred mice and humans, and so have recently started make mouse spleen organoids so that we can analyze their vaccine responses alongside human spleens. With the advanced single cell analysis tools available it should be relatively straightforward to identify differences. We can then follow up those differences with gene editing using CRISPR-Cas9, as we have done recently. We will also serve as a resource for all three of the main projects, using gene editing and other methods with organoids for Dr. Wang and Khatri’s projects, as well has interrogating spleen organoids from high and low BMI individuals in collaboration with those projects and for quickly testing novel immunogens with Dr. Barnes... ## Key facts - **NIH application ID:** 10825318 - **Project number:** 2U19AI057229-21 - **Recipient organization:** STANFORD UNIVERSITY - **Principal Investigator:** Mark Morris Davis - **Activity code:** U19 (R01, R21, SBIR, etc.) - **Funding institute:** NIH - **Fiscal year:** 2024 - **Award amount:** $553,826 - **Award type:** 2 - **Project period:** 2003-09-01 → 2029-04-30 ## Primary source NIH RePORTER: https://reporter.nih.gov/project-details/10825318 ## Citation > US National Institutes of Health, RePORTER application 10825318, Advancing immune organoid technology and organoid combinations (2U19AI057229-21). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10825318. Licensed CC0. --- *[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*