# Identification of targets of CD4 and CD8 T cell reactivity conserved across Sarbecoviruses and recognized across different animal species

> **NIH NIH P01** · WASHINGTON UNIVERSITY · 2022 · $1,946,055

## Abstract

PROJECT SUMMARY
The overarching goal of Project 2 is to discover and design vaccine antigen candidates that confer broad cross-
protective T cell immunity to multiple coronavirus (CoV) species with pandemic potential. Cross-reactivity at the
T cell level has been unequivocally demonstrated between SARS-CoV-2, other Sarbecoviruses, and other more
distantly related CoV in our previous studies. By incorporating strategies that explicitly elicit cellular immunity
into vaccines generated by Project 3, cross-protection against future pandemics emerging from CoV reservoirs
may be possible. Specific Aim 1 will define targets of CD4+ and CD8+ T cell reactivity that are broadly
conserved across different Sarbecoviruses, Merbecoviruses, and other betacoronaviruses of concern
by (i) identifying conserved regions across the entire CoV proteome, including all mature non-structural proteins
(nsp) and open reading frames (ORFs) for each of these taxonomic groups, (ii) performing a meta-analysis of
immunogenicity data to catalog known T cell epitopes for these antigens to define which antigen subregions are
recognized following natural infection by different CoV species, and (iii) integrating these data to select a set of
candidate conserved T cell epitope regions from each of the three taxonomic groups for experimental evaluation.
This bioinformatic analysis will assign specific quantitative scores, including sequence conservation scores,
human immunogenicity scores, and cross-reactivity for human T cells scores to various proteins subregions.
Specific Aim 2 will test human T cells directed against epitopes from Aim 1 for their capacity to recognize
homologous sequences from different Sarbecoviruses, Merbecoviruses, and other betacoronaviruses
of concern by (i) synthesizing the conserved epitope regions defined in Aim 1 from prototype viruses and
homologous peptides from each of the different taxonomic groups evaluated in Aim 1, (ii) eliciting T cell lines
from COVID-19 convalescent human donors and human subjects with NL63 and OC43-reactive memory T cells
using SARS-CoV-2-, NL63-, and OC43-derived epitopes, (iii) testing these epitope-specific T cell lines for cross-
reactivity with corresponding homologous peptides from each of the three taxonomic groups using an approach
developed in our laboratory to evaluate CoV cross-reactivity, and (iv) performing bioinformatic analyses to predict
immunogenicity in our rodent models. Based on this experimental work, we will prioritize potential candidates,
and deliver lists of candidates to the overall Program lead in Core A for incorporation into two vaccine platforms
in Project 3 and testing for immunogenicity and cross-protection in Core B. This project will produce the first
comprehensive evaluation of T cell immunogenicity of the entire CoV proteome across a broad cross-
section of CoVs with pandemic potential using a tight integration of bioinformatics prediction and
experimental validation to create antigens for va...

## Key facts

- **NIH application ID:** 10420515
- **Project number:** 1P01AI168347-01
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Alba Grifoni
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $1,946,055
- **Award type:** 1
- **Project period:** 2022-09-02 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10420515

## Citation

> US National Institutes of Health, RePORTER application 10420515, Identification of targets of CD4 and CD8 T cell reactivity conserved across Sarbecoviruses and recognized across different animal species (1P01AI168347-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10420515. Licensed CC0.

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