Comparison of two T-cell assays to evaluate T-cell responses to SARS-CoV-2 following vaccination in naïve and convalescent healthcare workers

PITCH Consortium

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Abstract

T-cell responses to SARS-CoV-2 following infection and vaccination are less characterized than antibody responses, due to a more complex experimental pathway. We measured T-cell responses in 108 healthcare workers (HCWs) using the commercialized Oxford Immunotec T-SPOT Discovery SARS-CoV-2 assay service (OI T-SPOT) and the PITCH ELISpot protocol established for academic research settings. Both assays detected T-cell responses to SARS-CoV-2 spike, membrane, and nucleocapsid proteins. Responses were significantly lower when reported by OI T-SPOT than by PITCH ELISpot. Four weeks after two doses of either Pfizer/BioNTech BNT162b or ChAdOx1 nCoV-19 AZD1222 vaccine, the responder rate was 63% for OI T-SPOT Panels 1 + 2 (peptides representing SARS-CoV-2 spike protein excluding regions present in seasonal coronaviruses), 69% for OI T-SPOT Panel 14 (peptides representing the entire SARS-CoV-2 spike), and 94% for the PITCH ELISpot total spike. The two OI T-SPOT panels correlated strongly with each other showing that either readout quantifies spike-specific T-cell responses, although the correlation between the OI T-SPOT panels and the PITCH ELISpot total spike was moderate. The standardization, relative scalability, and longer interval between blood acquisition and processing are advantages of the commercial OI T-SPOT assay. However, the OI T-SPOT assay measures T-cell responses at a significantly lower magnitude compared to the PITCH ELISpot assay, detecting T-cell responses in a lower proportion of vaccinees. This has implications for the reporting of low-level T-cell responses that may be observed in patient populations and for the assessment of T-cell durability after vaccination.

Original languageEnglish
Pages (from-to)90-98
Number of pages9
JournalClinical and Experimental Immunology
Volume209
Issue number1
DOIs
Publication statusPublished - 1 Jul 2022

Bibliographical note

Funding Information:
This work was funded by the National Core Study: Immunity (NCSi4P programme) "Optimal cellular assays for SARSCoV-2 T cell, B cell and innate immunity" and by the UK Department of Health and Social Care as part of the PITCH (Protective Immunity from T cells to Covid-19 in Health workers) Consortium, with contributions from UKRI/NIHR through the UK Coronavirus Immunology Consortium (UK-CIC), the Huo Family Foundation and The National Institute for Health Research (UKRIDHSC COVID-19 Rapid Response Rolling Call, Grant Reference Number COV19-RECPLAS). A.A. is funded by a Wellcome Clinical Research Training Fellowship (216417/Z/19/Z). E.B. and P.K. are NIHR Senior Investigators and P.K. is funded by WT109965MA. S.J.D. is funded by an NIHR Global Research Professorship (NIHR300791). D.S. is supported by the NIHR Academic Clinical Lecturer programme in Oxford. LT is supported by a Wellcome Trust fellowship [205228/Z/16/Z]. For the purpose of Open Access, the authors have applied a CC BY public copyright licence to any Author Accepted Manuscript version arising from this submission. LT is also supported by the US Food and Drug Administration Medical Countermeasures Initiative contract 75F40120C00085 and by the National Institute for Health Research Health Protection Research Unit (HPRU) in Emerging and Zoonotic Infections (NIHR200907) at the University of Liverpool in partnership with Public Health England (PHE), in collaboration with Liverpool School of Tropical Medicine and the University of Oxford. LT is based at the University of Liverpool. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR, the Department of Health and Social Care or UKHSA, or the US Food and Drug Administration.

Publisher Copyright:
© 2022 The Author(s).

Keywords

  • SARS-CoV-2
  • T cell
  • infection
  • vaccination
  • virus

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