# C19 SARS-CoV-2-specific T cells in the infected nasel epithelium

> **NIH NIH R21** · UNIVERSITY OF WASHINGTON · 2021 · $264,749

## Abstract

Summary
The acquired, antigen-specific immune response to SARS-CoV-2-infection is likely central to
determining the outcome of COVID-19 and the efficacy and durability of vaccination. CD4 T cell
help is required for lasting, avid antibody responses. The leading vaccine candidates include
some formats that can also induce CD8 T cells, such as viral vectors and nucleic acids, and
other formats such as adjuvanted protein that cannot. Compelling evidence for an antiviral
effects of virus-specific CD8 T cells could tilt the balance in favor of CD8-eliciting vaccine
platforms. Aim 1 and Aim 2 of this exploratory R21 on the T cell response to SARS-CoV-2
concern CD8- and CD4 T cell responses, respectively. Upper and lower airway respiratory
epithelium are the primary target tissues for SARS-CoV-2. The nasal epithelium is particularly
rich in expression of ACE2 and TMPRSS2, host molecules required for viral entry. We leverage
Co-Investigator Abuzeid’s experience in harvesting nasal cells and expanding primary nasal
epithelial cells (HNEpC) and Collaborator Greninger’s expertise in BSL3 virology and
quantitative RNA measurement to create systems to study T cell-infected epithelial cell
interactions in vitro. We use our large COVID-19 biobank, in-lab experience, and other NIAID
resources to generate functionally unlimited amounts of highly avid SARS-CoV-2-specific CD8
and CD4 T cells with precisely known HLA restriction and defined peptide targets. Infection of
HNEpC will be carefully characterized and optimized. We will then measure T cell effector
functions including the killing of infected cells, reduction of viral progeny output, and cytokine
release. In follow-up studies, we hope to leverage SARS-CoV-2 genetic systems to make
defined mutants in candidate immune evasion genes and extend our studies to lower respiratory
tract cells and organoids. Overall, we strive to model important interactions between immune
cells and the SARS-CoV-2 infected respiratory tract.
Relevance
Vaccines may need to elicit SARS-CoV-2 specific T cells that can quickly recognize SARS-CoV-
2-specific infected upper respiratory tract epithelial cells and shut down their production of
progeny virus, to both limit the progression of infection and symptoms within patients, and
reduce the shedding of infectious virus that may infect other persons. In this R21 grant
application, we will use established, working methods to isolate large quantities of pure SARS-
CoV-2-specific T cells from recovered persons and study their ability to exert anti-viral effects
using cell cultures of the cells that line the nasal cavity that are normally infected during COVID-
19.

## Key facts

- **NIH application ID:** 10285229
- **Project number:** 1R21AI163999-01
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **Principal Investigator:** David M Koelle
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $264,749
- **Award type:** 1
- **Project period:** 2021-06-15 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10285229

## Citation

> US National Institutes of Health, RePORTER application 10285229, C19 SARS-CoV-2-specific T cells in the infected nasel epithelium (1R21AI163999-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10285229. Licensed CC0.

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