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

doi:10.1016/j.celrep.2023.112470

Evaluation of T cell responses to naturally processed variant SARS-CoV-2 spike antigens in individuals following infection or vaccination

Cell Rep. 2023 May 30;42(5):112470. doi: 10.1016/j.celrep.2023.112470. Epub 2023 Apr 21.

Authors

Zixi Yin¹, Ji-Li Chen¹, Yongxu Lu², Beibei Wang³, Leila Godfrey⁴, Alexander J Mentzer⁵, Xuan Yao³, Guihai Liu⁶, Dannielle Wellington³, Yiqi Zhao², Peter A C Wing⁷, Wanwisa Dejnirattisa⁸, Piyada Supasa⁵, Chang Liu⁹, Philip Hublitz¹⁰, Ryan Beveridge¹¹, Craig Waugh¹², Sally-Ann Clark¹², Kevin Clark¹², Paul Sopp¹², Timothy Rostron¹³, Juthathip Mongkolsapaya⁹, Gavin R Screaton⁹, Graham Ogg¹, Katie Ewer¹⁴, Andrew J Pollard¹⁵, Sarah Gilbert¹⁶, Julian C Knight⁹, Teresa Lambe¹⁷, Geoffrey L Smith¹⁸, Tao Dong¹⁹, Yanchun Peng²⁰

Affiliations

¹ 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.
² Department of Pathology, University of Cambridge, Cambridge CB2 1QP, UK.
³ Chinese Academy of Medical Science (CAMS) Oxford Institute (COI), University of Oxford, Oxford OX3 7FZ, UK.
⁴ Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford OX3 7LE, UK.
⁵ Wellcome Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK; Nuffield Department of Medicine, University of Oxford, Oxford OX3 7BN, UK.
⁶ 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.
⁷ 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.
⁸ 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.
⁹ 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.
¹⁰ Genome Engineering Facility, MRC Weatherall Institute of Molecular Medicine, University of Oxford, Oxford OX3 9DS, UK.
¹¹ Screening Facility, MRC Weatherall Institute of Molecular Medicine, University of Oxford, Oxford OX3 9DS, UK.
¹² Flow Cytometry Facility, MRC Weatherall Institute of Molecular Medicine, University of Oxford, Oxford OX3 9DS, UK.
¹³ Sequencing Facility, MRC Weatherall Institute of Molecular Medicine, University of Oxford, Oxford OX3 9DS, UK.
¹⁴ Nuffield Department of Medicine, University of Oxford, Oxford OX3 7BN, UK.
¹⁵ 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.
¹⁶ Chinese Academy of Medical Science (CAMS) Oxford Institute (COI), University of Oxford, Oxford OX3 7FZ, UK; Pandemic Sciences Institute, University of Oxford, Oxford, UK.
¹⁷ 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. Electronic address: teresa.lambe@paediatrics.ox.ac.uk.
¹⁸ Department of Pathology, University of Cambridge, Cambridge CB2 1QP, UK. Electronic address: geoffrey.smith@path.ox.ac.uk.
¹⁹ 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. Electronic address: tao.dong@imm.ox.ac.uk.
²⁰ 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. Electronic address: yanchun.peng@imm.ox.ac.uk.

Abstract

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.

Keywords: CP: Immunology; ChAdOx1 nCoV-19; SARS-CoV-2; T cell; antigen processing and presentation; immune escape; recombinant vaccinia virus; spike protein; variants of concern.

Publication types

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

MeSH terms

Antibodies, Viral
COVID-19*
ChAdOx1 nCoV-19
Humans
SARS-CoV-2*
Vaccination

Substances

spike protein, SARS-CoV-2
ChAdOx1 nCoV-19
Antibodies, Viral

Grants and funding

WT_/Wellcome Trust/United Kingdom