Development of a peptide-based vaccine using a T cell epitope derived from SARS-CoV-2

Satoshi Baba; Hiroki Hayashi; Shota Yoshida; Nanxiang Yin; Munehisa Shimamura; Ryuichi Morishita; Hiromi Rakugi; Hironori Nakagami; Koichi Yamamoto

doi:10.1016/j.isci.2025.112542

Development of a peptide-based vaccine using a T cell epitope derived from SARS-CoV-2

iScience. 2025 Apr 28;28(6):112542. doi: 10.1016/j.isci.2025.112542. eCollection 2025 Jun 20.

Authors

Satoshi Baba^{1

2}, Hiroki Hayashi¹, Shota Yoshida^{1

2}, Nanxiang Yin^{1

2}, Munehisa Shimamura^{3

4}, Ryuichi Morishita⁵, Hiromi Rakugi^{2

6}, Hironori Nakagami^{1

7}, Koichi Yamamoto²

Affiliations

¹ Department of Health Development and Medicine, Osaka University, Suita, Osaka, Japan.
² Department of Geriatric Medicine, Osaka University, Suita, Osaka, Japan.
³ Department of Gene & Stem Cell Regenerative Therapy, Osaka University, Suita, Osaka, Japan.
⁴ Department of Neurology, Osaka University, Suita, Osaka, Japan.
⁵ Department of Clinical Gene Therapy, Osaka University, Suita, Osaka, Japan.
⁶ Osaka Rosai Hospital, Sakai, Osaka, Japan.
⁷ Center for Infectious Disease Education and Research (CiDER), Osaka University, Suita, Osaka, Japan.

Abstract

Follicular helper T (Tfh) cells are a subset of CD4⁺ T cells that help B cells to produce high-affinity antibodies. Efficient Tfh cell induction by vaccines is critical for protective efficacy against diseases. A Tfh epitope, identified from the SARS-CoV-2 spike protein, has been shown to bind to the corresponding HLA and activates Tfh cells. Here, we assessed the efficacy of a peptide vaccine conjugated with SARS-CoV-2 Tfh epitope against experimental hypertension in a mouse model. The Tfh-angiotensin II (Tfh-Ang II) vaccine activated Tfh and germinal center B cells and induced antibodies against Ang II, thereby suppressing hypertension. However, Ang II-specific autoreactive T cells were not induced. Interestingly, Tfh-Ang II-induced antibody production was enhanced by SARS-CoV-2 spike priming. Moreover, human peripheral blood mononuclear cells from individuals vaccinated with COVID-19 mRNA vaccine were activated by Tfh epitope. Collectively, the SARS-CoV-2 spike-derived universal Tfh epitope may be effective for peptide-based vaccine development.

Keywords: Immunology; Virology.