# Conserved CD8 T cell vaccines without B cell epitopes drive robust protection against SARS-CoV-2 that is enhanced by intranasal boost

## TL;DR

This study shows that vaccines targeting conserved CD8 T cell epitopes in SARS-CoV-2 offer strong protection, especially when boosted intranasally.

## Contribution

The study introduces a T cell-based vaccine strategy using conserved epitopes and demonstrates the effectiveness of intranasal boosting.

## Key findings

- Subcutaneous CD8 epitope vaccines reduced lung viral load and protected against low-dose SARS-CoV-2 challenge.
- Intranasal boosting enhanced lung resident memory T cells and provided durable protection against high-dose infection.
- T cell vaccines targeting conserved epitopes may offer broad immunity against SARS-CoV-2 and other respiratory viruses.

## Abstract

The emergence of SARS-CoV-2 variants has challenged the current spike protein–focused COVID-19 vaccine strategy due to neutralizing antibody escape and waning antibody-mediated immunity. In contrast, T cell–mediated immunity targeting conserved epitopes may offer broad and long-lasting protection. However, whether T cells alone can provide sufficient protection remains unclear. Here, we identified both Omicron BA.1–specific and ancestral (Wuhan)–conserved CD8 T cell epitopes in the SARS-CoV-2 spike protein and evaluated them as carrier-protein fusion vaccines in mouse models. Subcutaneous immunizations with two CD8 epitope peptides substantially lowered lung viral load and conferred protection against low-dose viral challenge, but not against high-dose challenge. Notably, intranasal boosting—with or without adjuvant—enhanced lung resident memory T cell responses and conferred potent, durable protection against high-dose infection. These findings emphasize the importance of mucosal vaccination to boost protective T cell immunity against SARS-CoV-2 and support the potential of T cell–based vaccines targeting conserved epitopes for broad immunity against SARS-CoV-2 and other respiratory viral threats.

Conserved CD8 T cell vaccines provide robust protection against SARS-CoV-2 that is enhanced by intranasal boosting.