# Using a tonsil organoid system to probe conditions for the induction of protective antibody and T cell responses to influenza.

> **NIH NIH U19** · STANFORD UNIVERSITY · 2023 · $410,356

## Abstract

PROJECT SUMMARY
Influenza is a serious public health issue; vulnerable populations, including young children and the elderly, are
especially at risk of influenza-related morbidity and mortality. Due to antigenic drift and shift of the virus as well
as poor vaccine efficacy in older people, current immunization efforts fall substantially short of providing
protection to the population. Research toward developing a universal influenza vaccine have been hindered by
a lack of methods to model the human adaptive immune response. In this context, we have recently developed
a tonsil organoid system using discarded human tonsil cells from sleep apnea patients that recapitulates at
least some of the key features of an adaptive immune response against influenza, including high affinity
antibodies specific for Influenza antigens and the HA molecule. We believe that this fully human system will be
an ideal platform to explore and manipulate the anti-flu response in humans. In Aim 1, we will identify the
minimal cellular requirements to develop protective influenza-specific T and B cell responses using these
organoids. In Aim 2 we will investigate the immunomodulatory effects of adjuvants, particularly whether they
influence the specificity, diversity or affinity of the influenza response. In Aim 3 we will manipulate the
expression of particular genes that are likely to be important in the antibody and T cell responses and which
address specific hypotheses-such as does AID play a major role in this response with respect to the specific
antibodies that are generated in this system? Other genes that might alter the affinity or glycosylation pattern of
the antibodies will also be investigated, as well as at least one that characterizes a uniquely flu specific
response (CD38) and is expressed in germinal centers. In Aim 4 we combine computational modeling with
nanoparticle and virosome stimulation of these organoids, test hypotheses about the optimal density of HA
head vs stem constructs in order skew the antibody response towards broadly neutralizing, high affinity
antibodies. These data could significantly aid the formulation of new vaccine strategies for the much hoped for
universal flu vaccine.

## Key facts

- **NIH application ID:** 10656182
- **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:** $410,356
- **Award type:** 5
- **Project period:** 2003-09-30 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10656182

## Citation

> US National Institutes of Health, RePORTER application 10656182, Using a tonsil organoid system to probe conditions for the induction of protective antibody and T cell responses to influenza. (5U19AI057229-20). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10656182. Licensed CC0.

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