Functional changes in cytotoxic CD8+ T-cell cross-reactivity against the SARS-CoV-2 Omicron variant after mRNA vaccination

Takuto Nogimori; Koichiro Suzuki; Yuji Masuta; Ayaka Washizaki; Mika Yagoto; Mami Ikeda; Yuki Katayama; Hidenori Kanda; Minoru Takada; Shohei Minami; Takeshi Kobayashi; Shokichi Takahama; Yasuo Yoshioka; Takuya Yamamoto

doi:10.3389/fimmu.2022.1081047

Functional changes in cytotoxic CD8+ T-cell cross-reactivity against the SARS-CoV-2 Omicron variant after mRNA vaccination

Front Immunol. 2023 Jan 4:13:1081047. doi: 10.3389/fimmu.2022.1081047. eCollection 2022.

Authors

Takuto Nogimori^{1

2}, Koichiro Suzuki³, Yuji Masuta^{1

4}, Ayaka Washizaki^{1

2}, Mika Yagoto¹, Mami Ikeda¹, Yuki Katayama¹, Hidenori Kanda⁵, Minoru Takada⁶, Shohei Minami⁷, Takeshi Kobayashi⁷, Shokichi Takahama^{1

2}, Yasuo Yoshioka^{3

8

9

10}, Takuya Yamamoto^{1

2

4

7

11}

Affiliations

¹ Laboratory of Immunosenescence, Center for Vaccine and Adjuvant Research, National Institutes of Biomedical Innovation, Health and Nutrition, Osaka, Japan.
² Research Institute for Microbial Diseases, Osaka University, Osaka, Japan.
³ The Research Foundation for Microbial Diseases of Osaka University (BIKEN), Osaka, Japan.
⁴ Laboratory of Aging and Immune Regulation, Graduate School of Pharmaceutical Sciences, Osaka University, Osaka, Japan.
⁵ KINSHUKAI, Hanwa Memorial Hospital, Osaka, Japan.
⁶ KINSHUKAI, Hanwa The Second Senboku Hospital, Osaka, Japan.
⁷ Department of Virology, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan.
⁸ Vaccine Creation Group, BIKEN Innovative Vaccine Research Alliance Laboratories, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan.
⁹ Laboratory of Nano-design for innovative drug development, Graduate School of Pharmaceutical Sciences, Osaka University, Osaka, Japan.
¹⁰ Institute for Open and Transdisciplinary Research Initiatives, Osaka University, Osaka, Japan.
¹¹ Department of Virology and Immunology, Graduate School of Medicine, Osaka University, Osaka, Japan.

Abstract

Understanding the T-cell responses involved in inhibiting COVID-19 severity is crucial for developing new therapeutic and vaccine strategies. Here, we characterized SARS-CoV-2 spike-specific CD8⁺ T cells in vaccinees longitudinally. The BNT162b2 mRNA vaccine can induce spike-specific CD8⁺ T cells cross-reacting to BA.1, whereas the T-cell receptor (TCR) repertoire usages decreased with time. Furthermore the mRNA vaccine induced spike-specific CD8⁺ T cells subpopulation expressing Granzyme A (GZMA), Granzyme B (GZMB) and Perforin simultaneously in healthy donors at 4 weeks after the second vaccination. The induced subpopulation was not maintained at 12 weeks after the second vaccination. Incorporating factors that efficiently induce CD8⁺ T cells with highly cytotoxic activity could improve future vaccine efficacy against such variants.

Keywords: COVID-19; SARS-CoV-2; TCR repertoire; cytotoxic T cells; mRNA vaccine.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antineoplastic Agents*
BNT162 Vaccine
CD8-Positive T-Lymphocytes
COVID-19* / prevention & control
Humans
RNA, Messenger / genetics
SARS-CoV-2
Vaccination

Substances

BNT162 Vaccine
Antineoplastic Agents
RNA, Messenger

Supplementary concepts

SARS-CoV-2 variants