# Features of Broad T Cell Coronavirus Immunity

> **NIH NIH P01** · BRIGHAM AND WOMEN'S HOSPITAL · 2021 · $2,572,892

## Abstract

Project 2 Summary
Coronavirus disease 2019 (COVID-19), caused by the SARS-CoV-2 coronavirus, has quickly become a global
health crisis of epic proportion. This pandemic, along with the SARS-CoV epidemic of 2002 and MERS-CoV
epidemic of 2012, highlights the tremendously dangerous ongoing threat to humanity posed by emerging
human-tropic coronaviruses that are transitioning from bats and other wildlife species into humans. Thus, while
early vaccines for SARS-CoV-2 have already demonstrated remarkable efficacy, next generation vaccines
should deliver broad protection against a wide spectrum of coronaviruses as well as improved robustness
against newly emerging SARS-CoV-2 variants that threaten immune escape. The overall goal of this program
is to design a pan-coronavirus vaccine strategy by coupling key immunological information regarding the B cell
and antibody response (Project 1) with the T cell response (Project 2) from SARS-CoV-2 infection and
vaccination to advanced structural design and vaccine delivery strategies (Project 3). This synergistic program
seeks to design a protective, durable vaccine able to induce immunity across a spectrum of human as well as
zoonotic coronaviruses. To do so will require a better understanding of the immunodominant epitopes targeted
by B cells and T cells as well as the extent of cross-reactivity these responses have against conserved
epitopes across coronavirus species. For T cells, which is the focus of Project 2, durable pan-coronavirus
immunity will likely require robust cross-reactive responses by multiple effector subsets, including T helper type
1 (TH1), T follicular helper (TFH), and cytotoxic T cells (CTL) generated in both circulating and respiratory
mucosal tissue-resident compartments. The overall goal of this project is to apply the knowledge gained from
our studies of SARS-CoV-2-specific T cells in convalescent COVID-19 patients and vaccinees as well as
innovative new experimental designs in mouse models to inform the design of vaccine immunogens by Project
3 that will maximize cross-reactive, yet durable and functionally diverse T cell immunity that will protect against
multiple coronaviruses. We hypothesize that the quality of T cell immunity to coronaviruses varies by epitope
and that pan-coronavirus vaccine design should incorporate epitopes based collectively on immunodominance,
functional diversity, and breadth of cross-reactivity. The studies in this project will identify the best epitopes for
this purpose. Specifically, we propose: 1) To identify SARS-CoV-2 CD4+ T cell epitopes from studies of
convalescent COVID-19 patients and vaccinees that exhibit the greatest extent of immunodominance,
durability, and cross-reactivity; 2) Evaluate the efficacy of cross-reactive CD4+ T cell epitopes in novel vaccine
immunogens to induce protective immune responses in animal models; and 3) Discover new MHC class I
epitopes using innovative screening technologies and evaluate their ability to generate pro...

## Key facts

- **NIH application ID:** 10328120
- **Project number:** 1P01AI165072-01
- **Recipient organization:** BRIGHAM AND WOMEN'S HOSPITAL
- **Principal Investigator:** ANDREW D LUSTER
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $2,572,892
- **Award type:** 1
- **Project period:** 2021-09-16 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10328120

## Citation

> US National Institutes of Health, RePORTER application 10328120, Features of Broad T Cell Coronavirus Immunity (1P01AI165072-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10328120. Licensed CC0.

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