Peptides Derived From S and N Proteins of Severe Acute Respiratory Syndrome Coronavirus 2 Induce T Cell Responses: A Proof of Concept for T Cell Vaccines

Yu Sun Lee, So Hee Hong, Hyo Jung Park, Ho Young Lee, Ji Yeon Hwang, Seo Yeon Kim, Jun Won Park, Kang Seuk Choi, Je Kyung Seong, Sang In Park, Sang Myeong Lee, Kyung Ah Hwang, Jun Won Yun, Jae Hwan Nam

Research output: Contribution to journalArticlepeer-review

Abstract

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants that escape vaccine-induced neutralizing antibodies has indicated the importance of T cell responses against this virus. In this study, we highlight the SARS-CoV-2 epitopes that induce potent T cell responses and discuss whether T cell responses alone are adequate to confer protection against SARS-CoV-2 and describe the administration of 20 peptides with an RNA adjuvant in mice. The peptides have been synthesized based on SARS-CoV-2 spike and nucleocapsid protein sequences. Our study demonstrates that immunization with these peptides significantly increases the proportion of effector memory T cell population and interferon-γ (IFN-γ)-, interleukin-4 (IL-4)-, tumor necrosis factor-α (TNF-α)-, and granzyme B-producing T cells. Of these 20 peptides, four induce the generation of IFN-γ-producing T cells, elicit CD8+ T cell (CTL) responses in a dose-dependent manner, and induce cytotoxic T lymphocytes that eliminate peptide-pulsed target cells in vivo. Although it is not statistically significant, these peptide vaccines reduce viral titers in infected hamsters and alleviate pulmonary pathology in SARS-CoV-2-infected human ACE2 transgenic mice. These findings may aid the design of effective SARS-CoV-2 peptide vaccines, while providing insights into the role of T cells in SARS-CoV-2 infection.

Original languageEnglish
Article number732450
JournalFrontiers in Microbiology
Volume12
DOIs
StatePublished - 24 Sep 2021

Keywords

  • CTL
  • SARS-CoV-2
  • T cell responses
  • peptides
  • vaccine

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