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Screening of HLA-A restricted T cell epitopes of SARS-CoV-2 and induction of CD8+ T cell responses in HLA-A transgenic mice

Xiaoxiao Jin, Ding Yan, Sun Shihui, Xinyi Wang, Zining Zhou, Xiaotao Liu, Miaomiao Li, Xian Chen, Anran Shen, Yandan Wu, Bicheng Liu, Jianqiong Zhang, Jian Li, Yi Yang, Haibo Qiu, View ORCID ProfileChuanlai Shen, Yuxian He, Guangyu Zhao
doi: https://doi.org/10.1101/2021.04.01.438020
Xiaoxiao Jin
1Department of Microbiology and Immunology, Medical School of Southeast University, Nanjing, Jiangsu, China 210009
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Ding Yan
1Department of Microbiology and Immunology, Medical School of Southeast University, Nanjing, Jiangsu, China 210009
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Sun Shihui
2State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, China 100071
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Xinyi Wang
1Department of Microbiology and Immunology, Medical School of Southeast University, Nanjing, Jiangsu, China 210009
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Zining Zhou
1Department of Microbiology and Immunology, Medical School of Southeast University, Nanjing, Jiangsu, China 210009
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Xiaotao Liu
1Department of Microbiology and Immunology, Medical School of Southeast University, Nanjing, Jiangsu, China 210009
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Miaomiao Li
3Blood Component Preparation Section, Jiangsu Province Blood Center, Nanjing, Jiangsu, China 210042
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Xian Chen
3Blood Component Preparation Section, Jiangsu Province Blood Center, Nanjing, Jiangsu, China 210042
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Anran Shen
4Institute of Nephrology, Zhongda Hospital, Medical School of Southeast University, Nanjing, Jiangsu, China 210009
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Yandan Wu
1Department of Microbiology and Immunology, Medical School of Southeast University, Nanjing, Jiangsu, China 210009
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Bicheng Liu
4Institute of Nephrology, Zhongda Hospital, Medical School of Southeast University, Nanjing, Jiangsu, China 210009
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Jianqiong Zhang
1Department of Microbiology and Immunology, Medical School of Southeast University, Nanjing, Jiangsu, China 210009
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Jian Li
5Life Science & Technology School of Southeast University, Nanjing, Jiangsu, China 210096
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Yi Yang
6Jiangsu Province Key Laboratory of Critical Care Medicine, Department of Critical Care Medicine, Zhongda Hospital, Medical School of Southeast University, Nanjing, Jiangsu, China 210009
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Haibo Qiu
6Jiangsu Province Key Laboratory of Critical Care Medicine, Department of Critical Care Medicine, Zhongda Hospital, Medical School of Southeast University, Nanjing, Jiangsu, China 210009
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Chuanlai Shen
1Department of Microbiology and Immunology, Medical School of Southeast University, Nanjing, Jiangsu, China 210009
6Jiangsu Province Key Laboratory of Critical Care Medicine, Department of Critical Care Medicine, Zhongda Hospital, Medical School of Southeast University, Nanjing, Jiangsu, China 210009
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  • ORCID record for Chuanlai Shen
  • For correspondence: chuanlaishen@seu.edu.cn yhe@ipb.pumc.edu.cn guangyu0525@163.com
Yuxian He
7Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China 100730
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  • For correspondence: chuanlaishen@seu.edu.cn yhe@ipb.pumc.edu.cn guangyu0525@163.com
Guangyu Zhao
2State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, China 100071
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  • For correspondence: chuanlaishen@seu.edu.cn yhe@ipb.pumc.edu.cn guangyu0525@163.com
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Abstract

While SARS-CoV-2-specific T cells have been characterized to play essential roles in host immune protection in COVID-19 patients, few researches focus on the functional validation of T cell epitopes and development of vaccines inducing specific T cell responses. In this study, 120 CD8+ T cell epitopes from E, M, N, S and RdRp proteins of SARS-CoV-2 were validated by on-silicon prediction, DC-peptide-PBL costimulation with healthy donors’ PBMCs and HLA-A molecule competitive binding experiments. Among them, 110, 15, 6, 14 and 12 epitopes were highly homologous with SARS-CoV, OC43, NL63, HKU1, and 229E, respectively. Thirty-one epitopes restricted by HLA-A2 molecule were used to generate peptide cocktail vaccines in combination with Poly(I:C), R848 or polylactic-co-glycolic acid nanoparticles, which elicited robust specific CD8+ T cell responses in wild-type and HLA-A2/DR1 transgenic mice. Seven of the 31 epitopes were found to be cross-presented by HLA-A2 and H-2K/Db molecules. These data have provided a library of SARS-CoV-2 CD8+ T cell epitopes which restricted by a series of high-frequency HLA-A allotypes and covered broad population in Asia, and initially confirmed the feasibility of human MHC class I molecule-restricted SARS-CoV2 epitope peptide cocktail vaccines, thus will facilitate the development of T cell epitope vaccines and specific cellular function detection kits.

Competing Interest Statement

The authors have declared no competing interest.

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Posted April 01, 2021.
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Screening of HLA-A restricted T cell epitopes of SARS-CoV-2 and induction of CD8+ T cell responses in HLA-A transgenic mice
Xiaoxiao Jin, Ding Yan, Sun Shihui, Xinyi Wang, Zining Zhou, Xiaotao Liu, Miaomiao Li, Xian Chen, Anran Shen, Yandan Wu, Bicheng Liu, Jianqiong Zhang, Jian Li, Yi Yang, Haibo Qiu, Chuanlai Shen, Yuxian He, Guangyu Zhao
bioRxiv 2021.04.01.438020; doi: https://doi.org/10.1101/2021.04.01.438020
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Screening of HLA-A restricted T cell epitopes of SARS-CoV-2 and induction of CD8+ T cell responses in HLA-A transgenic mice
Xiaoxiao Jin, Ding Yan, Sun Shihui, Xinyi Wang, Zining Zhou, Xiaotao Liu, Miaomiao Li, Xian Chen, Anran Shen, Yandan Wu, Bicheng Liu, Jianqiong Zhang, Jian Li, Yi Yang, Haibo Qiu, Chuanlai Shen, Yuxian He, Guangyu Zhao
bioRxiv 2021.04.01.438020; doi: https://doi.org/10.1101/2021.04.01.438020

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