# Factors influencing TRM responses in upper airway tissue

> **NIH NIH U19** · LA JOLLA INSTITUTE FOR IMMUNOLOGY · 2024 · $721,915

## Abstract

PROJECT SUMMARY
The La Jolla CCHI team will investigate pathogen-specific memory T and B cell responses in the blood, and in
lymphoid and non-lymphoid tissues in the upper airways, where many airborne infectious pathogens entry and
replicate. In Project 3, we will focus on understanding the factors (smoking status, older age, diabetes,
vaccination) associated with the magnitude, persistence and quality of pathogen-specific tissue-resident memory
T cells (TRM cells) in the upper airway tissue. Upper airway TRM cells play important roles in protection against
infection by airborne pathogens. Despite their importance, very little is known about the factors like vaccination
routes, co-morbidities like age, diabetes, smoking status that influence the generation of pathogen/vaccine-
specific TRM cells in human upper airway tissue. We have extensive expertise in understanding the biology of
TRM cells, having shown their importance in driving anti-PD1 therapy T cell responses in human cancers. Here,
we will examine the biology of infection-elicited and vaccine-elicited TRM cells in upper airway tissue samples
obtained during routine surgery from 200 living donors. These donors are relatively fit for elective surgery and
are enrolled in TARGET head and neck study, a prospective observational study that grows by ~20 cases/month
at tertiary health centers, and now includes vaccination (TARGET vaccination) as an intervention prior to surgery.
Our studies will expand well beyond SARS-CoV-2 to understand the diversity of TRM cells specific to viral
(Influenza, respiratory syncytial virus, parainfluenza, metapneumovirus, varicella zoster virus, human papilloma
virus), bacterial (pertussis) and fungal pathogens. Studies in Aim 1 will determine the correlation of three
important immunomodulating co-morbidities (smoking, older age and diabetes) with features (frequency,
phenotype and persistency) of pathogen/vaccine-specific TRM cells in the upper airway tissue. We will test the
hypothesis that key co-morbidities like smoking, older age and diabetes are associated with defects in pathogen-
specific TRM cell responses in airways. For studies in Aim 2, we will vaccinate donors 2-4 weeks prior to surgery
and determine vaccine-responsive TRM cells in upper airway tissue. We hypothesize that parenteral (i.m.)
vaccination can also induce/boost (pre-existing) TRM responses in the upper airways. This hypothesis is based
on recent studies in model organisms and humans, which suggests that parental vaccination may induce/boost
TRM responses in lungs. Because most donors would have had prior exposure to the antigens present in these
vaccines by either infection or vaccination – a real-life scenario – our analysis will largely assess effects on pre-
existing memory T cells. Overall, studies proposed in this Project that complement studies in Project 1 & 2 will
provide important insights into the nature of TRM responses in humans.

## Key facts

- **NIH application ID:** 10825346
- **Project number:** 2U19AI142742-06
- **Recipient organization:** LA JOLLA INSTITUTE FOR IMMUNOLOGY
- **Principal Investigator:** Pandurangan Vijayanand
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $721,915
- **Award type:** 2
- **Project period:** 2019-03-11 → 2029-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10825346

## Citation

> US National Institutes of Health, RePORTER application 10825346, Factors influencing TRM responses in upper airway tissue (2U19AI142742-06). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10825346. Licensed CC0.

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