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Different pattern of pre-existing SARS-COV-2 specific T cell immunity in SARS-recovered and uninfected individuals

Nina Le Bert, Anthony T Tan, Kamini Kunasegaran, Christine Y L Tham, Morteza Hafezi, Adeline Chia, Melissa Chng, Meiyin Lin, Nicole Tan, Martin Linster, Wan Ni Chia, Mark I-Cheng Chen, Lin-Fa Wang, Eng Eong Ooi, Shirin Kalimuddin, Paul Anantharajal Tambyah, Jenny Guek-Hong Low, Yee-Joo Tan, View ORCID ProfileAntonio Bertoletti
doi: https://doi.org/10.1101/2020.05.26.115832
Nina Le Bert
1Emerging Infectious Diseases Program, Duke-NUS Medical School, Singapore
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Anthony T Tan
1Emerging Infectious Diseases Program, Duke-NUS Medical School, Singapore
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Kamini Kunasegaran
1Emerging Infectious Diseases Program, Duke-NUS Medical School, Singapore
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Christine Y L Tham
1Emerging Infectious Diseases Program, Duke-NUS Medical School, Singapore
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Morteza Hafezi
1Emerging Infectious Diseases Program, Duke-NUS Medical School, Singapore
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Adeline Chia
1Emerging Infectious Diseases Program, Duke-NUS Medical School, Singapore
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Melissa Chng
1Emerging Infectious Diseases Program, Duke-NUS Medical School, Singapore
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Meiyin Lin
1Emerging Infectious Diseases Program, Duke-NUS Medical School, Singapore
2Institute of Molecular and Cell Biology (IMCB), A*STAR, Singapore
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Nicole Tan
1Emerging Infectious Diseases Program, Duke-NUS Medical School, Singapore
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Martin Linster
1Emerging Infectious Diseases Program, Duke-NUS Medical School, Singapore
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Wan Ni Chia
1Emerging Infectious Diseases Program, Duke-NUS Medical School, Singapore
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Mark I-Cheng Chen
3National Center of Infectious Diseases, Singapore
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Lin-Fa Wang
1Emerging Infectious Diseases Program, Duke-NUS Medical School, Singapore
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Eng Eong Ooi
1Emerging Infectious Diseases Program, Duke-NUS Medical School, Singapore
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Shirin Kalimuddin
4Department of Infectious Diseases, Singapore General Hospital, Singapore
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Paul Anantharajal Tambyah
5Infectious Disease, Department of Medicine, National University Hospital, Singapore
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Jenny Guek-Hong Low
1Emerging Infectious Diseases Program, Duke-NUS Medical School, Singapore
4Department of Infectious Diseases, Singapore General Hospital, Singapore
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Yee-Joo Tan
2Institute of Molecular and Cell Biology (IMCB), A*STAR, Singapore
6Infectious Diseases Programme, Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
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Antonio Bertoletti
1Emerging Infectious Diseases Program, Duke-NUS Medical School, Singapore
7Singapore Immunology Network, A*STAR, Singapore
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  • ORCID record for Antonio Bertoletti
  • For correspondence: antonio@duke-nus.edu.sg
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Abstract

Memory T cells induced by previous infections can influence the course of new viral infections. Little is known about the pattern of SARS-CoV-2 specific pre-existing memory T cells in human. Here, we first studied T cell responses to structural (nucleocapsid protein, NP) and non-structural (NSP-7 and NSP13 of ORF1) regions of SARS-CoV-2 in convalescent from COVID-19 (n=24). In all of them we demonstrated the presence of CD4 and CD8 T cells recognizing multiple regions of the NP protein. We then show that SARS-recovered patients (n=23), 17 years after the 2003 outbreak, still possess long-lasting memory T cells reactive to SARS-NP, which displayed robust cross-reactivity to SARS-CoV-2 NP. Surprisingly, we observed a differential pattern of SARS-CoV-2 specific T cell immunodominance in individuals with no history of SARS, COVID-19 or contact with SARS/COVID-19 patients (n=18). Half of them (9/18) possess T cells targeting the ORF-1 coded proteins NSP7 and 13, which were rarely detected in COVID-19- and SARS-recovered patients. Epitope characterization of NSP7-specific T cells showed recognition of protein fragments with low homology to “common cold” human coronaviruses but conserved among animal betacoranaviruses.

Thus, infection with betacoronaviruses induces strong and long-lasting T cell immunity to the structural protein NP. Understanding how pre-existing ORF-1-specific T cells present in the general population impact susceptibility and pathogenesis of SARS-CoV-2 infection is of paramount importance for the management of the current COVID-19 pandemic.

Competing Interest Statement

A.B. is a cofounder of Lion TCR, a biotech company developing T cell receptors for treatment of virus-related diseases and cancers. None of the other authors has any competing interest related to the study.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted May 27, 2020.
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Different pattern of pre-existing SARS-COV-2 specific T cell immunity in SARS-recovered and uninfected individuals
Nina Le Bert, Anthony T Tan, Kamini Kunasegaran, Christine Y L Tham, Morteza Hafezi, Adeline Chia, Melissa Chng, Meiyin Lin, Nicole Tan, Martin Linster, Wan Ni Chia, Mark I-Cheng Chen, Lin-Fa Wang, Eng Eong Ooi, Shirin Kalimuddin, Paul Anantharajal Tambyah, Jenny Guek-Hong Low, Yee-Joo Tan, Antonio Bertoletti
bioRxiv 2020.05.26.115832; doi: https://doi.org/10.1101/2020.05.26.115832
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Different pattern of pre-existing SARS-COV-2 specific T cell immunity in SARS-recovered and uninfected individuals
Nina Le Bert, Anthony T Tan, Kamini Kunasegaran, Christine Y L Tham, Morteza Hafezi, Adeline Chia, Melissa Chng, Meiyin Lin, Nicole Tan, Martin Linster, Wan Ni Chia, Mark I-Cheng Chen, Lin-Fa Wang, Eng Eong Ooi, Shirin Kalimuddin, Paul Anantharajal Tambyah, Jenny Guek-Hong Low, Yee-Joo Tan, Antonio Bertoletti
bioRxiv 2020.05.26.115832; doi: https://doi.org/10.1101/2020.05.26.115832

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