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

  1. Eloise Phillips
  2. Sandra Adele
  3. Tom Malone
  4. Alexandra Deeks
  5. Lizzie Stafford
  6. Susan L Dobson
  7. Ali Amini
  8. Donal Skelly
  9. David Eyre
  10. Katie Jeffery
  11. Christopher P Conlon
  12. Christina Dold
  13. Ashley Otter
  14. Silvia D’Arcangelo
  15. Lance Turtle
  16. PITCH Consortium
  17. Eleanor Barnes
  18. Jeremy Chalk
  19. Susanna Dunachie
  20. Christopher Duncan
  21. Paul Klenerman
  22. Philippa Matthews
  23. Rebecca Payne
  24. Alex Richter
  25. Thushan de Silva
  26. Sarah Rowland-Jones
  27. Lance Turtle
  28. Dan Wootton
  29. Paul Klenerman
  30. Eleanor Barnes
  31. Susanna J Dunachie

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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.

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  1. Version published to 10.1093/cei/uxac042
  2. ScreenIT

    SciScore for 10.1101/2022.02.05.22270447: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    EthicsIRB: HCWs were enrolled in the OPTIC study (GI Biobank Study 16/YH/0247, approved by the research ethics committee (REC) at Yorkshire & The Humber - Sheffield Research Ethics Committee on 29 July 2016, and amended for the OPTIC study on 8 June 2020.
    Sex as a biological variableHealthy men and women aged 18 years and older were recruited, with all working HCWs eligible and outreach activities by the team to encourage participation from a wide range of age, sex, ethnicity and work role.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    Serological assays: Anti-spike (S) and anti-nucleocapsid (N) antibodies were measured using the Roche Elecsys® Anti-SARS-CoV-2 S and Roche Elecsys® Anti-SARS-CoV-2 N assays at the Public Health England (now United Kingdom Health Security Agency) Laboratories at Porton Down, UK.
    anti-nucleocapsid (N)
    suggested: None
    Software and Algorithms
    SentencesResources
    HCWs were enrolled in the OPTIC study (GI Biobank Study 16/YH/0247, approved by the research ethics committee (REC) at Yorkshire & The Humber - Sheffield Research Ethics Committee on 29 July 2016, and amended for the OPTIC study on 8 June 2020.
    OPTIC
    suggested: None
    Previous SARS-CoV-2 infection status was defined in HCWs based on documented PCR and/or baseline anti-S and anti-N serology results from the Abbott platform at Oxford University Hospital NHS Foundation Trust prior to vaccination.
    Abbott
    suggested: (Abbott, RRID:SCR_010477)
    Statistical analysis: Data was analysed in GraphPad Prism 9.1.2.
    GraphPad Prism
    suggested: (GraphPad Prism, RRID:SCR_002798)

    Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

    Results from LimitationRecognizer: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.

    Results from TrialIdentifier: No clinical trial numbers were referenced.

    Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

    Results from JetFighter: We did not find any issues relating to colormaps.

    Results from rtransparent:
    • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
    • Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
    • No protocol registration statement was detected.

    Results from scite Reference Check: We found no unreliable references.

    About SciScore

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  3. Version published to 10.1101/2022.02.05.22270447 on medRxiv