# Influenza responses and repertoire in vaccination, infection and tonsil organoids.

> **NIH NIH U19** · STANFORD UNIVERSITY · 2023 · $2,207,151

## Abstract

Project Summary
Influenza remains a continual threat to health of many Americans, resulting in 9.2-35.6 million
illnesses, 140,000-710,000 hospitalizations, and 12,000-56,000 deaths annually since 2010
(CDC), as well as the ever-present likelihood of a devastating pandemic that could kill millions.
Recent work has also suggested that a universal flu vaccine may be possible, although there is
considerable uncertainty about how to achieve this. This renewal application seeks to leverage
some of the important methodologies and data that we have developed in this past granting
period to understand at a much deeper level what constitutes broad and effective B and T cell
responses against influenza so as to better inform next generation vaccine efforts. Specifically,
we have developed a unique tonsil organoid system that we can expose to a flu vaccine and
produce high affinity antibodies several days to a week later. This gives us an ability to
manipulate and test vaccine constructs and adjuvants in a fully human system in order to find
the best way to trigger broadly neutralizing antibodies. In addition, we have developed powerful
new T and B cell repertoire analysis methods that will allow us to productively analyze large flu-
specific TCR and Ig data sets to identify which specificities or other correlates contribute the
most to protection or amelioration of diseases in challenge studies. We also plan to further
analyze influenza vaccine responses in pregnant women, the elderly and twins, to test various
hypotheses that we have developed in our previous work in the CCHI. Lastly we will take
advantage of recent advances by the Nolan lab in imaging tissue sections with large numbers of
different antibodies to analyze the cellular organization the tonsil organoids with time during a flu
vaccine response and after different interventions.

## Key facts

- **NIH application ID:** 10656176
- **Project number:** 5U19AI057229-20
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** Mark Morris Davis
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $2,207,151
- **Award type:** 5
- **Project period:** 2003-09-30 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10656176

## Citation

> US National Institutes of Health, RePORTER application 10656176, Influenza responses and repertoire in vaccination, infection and tonsil organoids. (5U19AI057229-20). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10656176. Licensed CC0.

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