Cell Reports (May 2023)
Evaluation of T cell responses to naturally processed variant SARS-CoV-2 spike antigens in individuals following infection or vaccination
- Zixi Yin,
- Ji-Li Chen,
- Yongxu Lu,
- Beibei Wang,
- Leila Godfrey,
- Alexander J. Mentzer,
- Xuan Yao,
- Guihai Liu,
- Dannielle Wellington,
- Yiqi Zhao,
- Peter A.C. Wing,
- Wanwisa Dejnirattisa,
- Piyada Supasa,
- Chang Liu,
- Philip Hublitz,
- Ryan Beveridge,
- Craig Waugh,
- Sally-Ann Clark,
- Kevin Clark,
- Paul Sopp,
- Timothy Rostron,
- Juthathip Mongkolsapaya,
- Gavin R. Screaton,
- Graham Ogg,
- Katie Ewer,
- Andrew J. Pollard,
- Sarah Gilbert,
- Julian C. Knight,
- Teresa Lambe,
- Geoffrey L. Smith,
- Tao Dong,
- Yanchun Peng
Affiliations
- Zixi Yin
- Chinese Academy of Medical Science (CAMS) Oxford Institute (COI), University of Oxford, Oxford OX3 7FZ, UK; MRC Human Immunology Unit, MRC Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford OX3 9DS, UK
- Ji-Li Chen
- Chinese Academy of Medical Science (CAMS) Oxford Institute (COI), University of Oxford, Oxford OX3 7FZ, UK; MRC Human Immunology Unit, MRC Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford OX3 9DS, UK
- Yongxu Lu
- Department of Pathology, University of Cambridge, Cambridge CB2 1QP, UK
- Beibei Wang
- Chinese Academy of Medical Science (CAMS) Oxford Institute (COI), University of Oxford, Oxford OX3 7FZ, UK
- Leila Godfrey
- Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford OX3 7LE, UK
- Alexander J. Mentzer
- Wellcome Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK; Nuffield Department of Medicine, University of Oxford, Oxford OX3 7BN, UK
- Xuan Yao
- Chinese Academy of Medical Science (CAMS) Oxford Institute (COI), University of Oxford, Oxford OX3 7FZ, UK
- Guihai Liu
- Chinese Academy of Medical Science (CAMS) Oxford Institute (COI), University of Oxford, Oxford OX3 7FZ, UK; Beijing You’an Hospital, Capital Medical University, Beijing 100069, China
- Dannielle Wellington
- Chinese Academy of Medical Science (CAMS) Oxford Institute (COI), University of Oxford, Oxford OX3 7FZ, UK
- Yiqi Zhao
- Department of Pathology, University of Cambridge, Cambridge CB2 1QP, UK
- Peter A.C. Wing
- Chinese Academy of Medical Science (CAMS) Oxford Institute (COI), University of Oxford, Oxford OX3 7FZ, UK; Nuffield Department of Medicine, University of Oxford, Oxford OX3 7BN, UK
- Wanwisa Dejnirattisa
- Wellcome Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK; Nuffield Department of Medicine, University of Oxford, Oxford OX3 7BN, UK; Division of Emerging Infectious Disease, Research Department, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand
- Piyada Supasa
- Wellcome Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK; Nuffield Department of Medicine, University of Oxford, Oxford OX3 7BN, UK
- Chang Liu
- Chinese Academy of Medical Science (CAMS) Oxford Institute (COI), University of Oxford, Oxford OX3 7FZ, UK; Wellcome Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK; Nuffield Department of Medicine, University of Oxford, Oxford OX3 7BN, UK
- Philip Hublitz
- Genome Engineering Facility, MRC Weatherall Institute of Molecular Medicine, University of Oxford, Oxford OX3 9DS, UK
- Ryan Beveridge
- Screening Facility, MRC Weatherall Institute of Molecular Medicine, University of Oxford, Oxford OX3 9DS, UK
- Craig Waugh
- Flow Cytometry Facility, MRC Weatherall Institute of Molecular Medicine, University of Oxford, Oxford OX3 9DS, UK
- Sally-Ann Clark
- Flow Cytometry Facility, MRC Weatherall Institute of Molecular Medicine, University of Oxford, Oxford OX3 9DS, UK
- Kevin Clark
- Flow Cytometry Facility, MRC Weatherall Institute of Molecular Medicine, University of Oxford, Oxford OX3 9DS, UK
- Paul Sopp
- Flow Cytometry Facility, MRC Weatherall Institute of Molecular Medicine, University of Oxford, Oxford OX3 9DS, UK
- Timothy Rostron
- Sequencing Facility, MRC Weatherall Institute of Molecular Medicine, University of Oxford, Oxford OX3 9DS, UK
- Juthathip Mongkolsapaya
- Chinese Academy of Medical Science (CAMS) Oxford Institute (COI), University of Oxford, Oxford OX3 7FZ, UK; Wellcome Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK; Nuffield Department of Medicine, University of Oxford, Oxford OX3 7BN, UK
- Gavin R. Screaton
- Chinese Academy of Medical Science (CAMS) Oxford Institute (COI), University of Oxford, Oxford OX3 7FZ, UK; Wellcome Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK; Nuffield Department of Medicine, University of Oxford, Oxford OX3 7BN, UK
- Graham Ogg
- Chinese Academy of Medical Science (CAMS) Oxford Institute (COI), University of Oxford, Oxford OX3 7FZ, UK; MRC Human Immunology Unit, MRC Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford OX3 9DS, UK
- Katie Ewer
- Nuffield Department of Medicine, University of Oxford, Oxford OX3 7BN, UK
- Andrew J. Pollard
- Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford OX3 7LE, UK; Pandemic Sciences Institute, University of Oxford, Oxford, UK; National Institute for Health Research Oxford Biomedical Research Center, Oxford, UK
- Sarah Gilbert
- Chinese Academy of Medical Science (CAMS) Oxford Institute (COI), University of Oxford, Oxford OX3 7FZ, UK; Pandemic Sciences Institute, University of Oxford, Oxford, UK
- Julian C. Knight
- Chinese Academy of Medical Science (CAMS) Oxford Institute (COI), University of Oxford, Oxford OX3 7FZ, UK; Wellcome Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK; Nuffield Department of Medicine, University of Oxford, Oxford OX3 7BN, UK
- Teresa Lambe
- Chinese Academy of Medical Science (CAMS) Oxford Institute (COI), University of Oxford, Oxford OX3 7FZ, UK; Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford OX3 7LE, UK; Pandemic Sciences Institute, University of Oxford, Oxford, UK; Corresponding author
- Geoffrey L. Smith
- Department of Pathology, University of Cambridge, Cambridge CB2 1QP, UK; Corresponding author
- Tao Dong
- Chinese Academy of Medical Science (CAMS) Oxford Institute (COI), University of Oxford, Oxford OX3 7FZ, UK; MRC Human Immunology Unit, MRC Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford OX3 9DS, UK; Corresponding author
- Yanchun Peng
- Chinese Academy of Medical Science (CAMS) Oxford Institute (COI), University of Oxford, Oxford OX3 7FZ, UK; MRC Human Immunology Unit, MRC Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford OX3 9DS, UK; Corresponding author
- Journal volume & issue
-
Vol. 42,
no. 5
p. 112470
Abstract
Summary: Most existing studies characterizing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific T cell responses are peptide based. This does not allow evaluation of whether tested peptides are processed and presented canonically. In this study, we use recombinant vaccinia virus (rVACV)-mediated expression of SARS-CoV-2 spike protein and SARS-CoV-2 infection of angiotensin-converting enzyme (ACE)-2-transduced B cell lines to evaluate overall T cell responses in a small cohort of recovered COVID-19 patients and uninfected donors vaccinated with ChAdOx1 nCoV-19. We show that rVACV expression of SARS-CoV-2 antigen can be used as an alternative to SARS-CoV-2 infection to evaluate T cell responses to naturally processed spike antigens. In addition, the rVACV system can be used to evaluate the cross-reactivity of memory T cells to variants of concern (VOCs) and to identify epitope escape mutants. Finally, our data show that both natural infection and vaccination could induce multi-functional T cell responses with overall T cell responses remaining despite the identification of escape mutations.
