Whole blood‐based measurement of SARS‐CoV‐2‐specific T cells reveals asymptomatic infection and vaccine immunogenicity in healthy subjects and patients with solid‐organ cancers

  1. Martin J. Scurr
  2. Wioleta M. Zelek
  3. George Lippiatt
  4. Michelle Somerville
  5. Stephanie E. A. Burnell
  6. Lorenzo Capitani
  7. Kate Davies
  8. Helen Lawton
  9. Thomas Tozer
  10. Tara Rees
  11. Kerry Roberts
  12. Mererid Evans
  13. Amanda Jackson
  14. Charlotte Young
  15. Lucy Fairclough
  16. Paddy Tighe
  17. Mark Wills
  18. Andrew D. Westwell
  19. B. Paul Morgan
  20. Awen Gallimore
  21. Andrew Godkin

Reviewed by

Read the full article See related articles

Listed in

Log in to save this article

Abstract

Accurate assessment of SARS‐CoV‐2 immunity is critical in evaluating vaccine efficacy and devising public health policies. Whilst the exact nature of effective immunity remains incompletely defined, SARS‐CoV‐2‐specific T‐cell responses are a critical feature that will likely form a key correlate of protection against COVID‐19. Here, we developed and optimized a high‐throughput whole blood‐based assay to determine the T‐cell response associated with prior SARS‐CoV‐2 infection and/or vaccination amongst 231 healthy donors and 68 cancer patients. Following overnight in vitro stimulation with SARS‐CoV‐2‐specific peptides, blood plasma samples were analysed for T H 1‐type cytokines. Highly significant differential IFN‐γ + /IL‐2 + SARS‐CoV‐2‐specific T‐cell responses were seen amongst previously infected COVID‐19‐positive healthy donors in comparison with unknown / naïve individuals ( p  < 0·0001). IFN‐γ production was more effective at identifying asymptomatic donors, demonstrating higher sensitivity (96·0% vs. 83·3%) but lower specificity (84·4% vs. 92·5%) than measurement of IL‐2. A single COVID‐19 vaccine dose induced IFN‐γ and/or IL‐2 SARS‐CoV‐2‐specific T‐cell responses in 116 of 128 (90·6%) healthy donors, reducing significantly to 27 of 56 (48·2%) when measured in cancer patients ( p  < 0·0001). A second dose was sufficient to boost T‐cell responses in the majority (90·6%) of cancer patients, albeit IFN‐γ + responses were still significantly lower overall than those induced in healthy donors ( p  = 0·034). Three‐month post‐vaccination T‐cell responses also declined at a faster rate in cancer patients. Overall, this cost‐effective standardizable test ensures accurate and comparable assessments of SARS‐CoV‐2‐specific T‐cell responses amenable to widespread population immunity testing, and identifies individuals at greater need of booster vaccinations.

Article activity feed

  1. Version published to 10.1111/imm.13433
  2. ScreenIT

    SciScore for 10.1101/2021.06.02.21258218: (What is this?)

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

    Table 1: Rigor

    EthicsIRB: This study received ethical approval from the Wales Cancer Bank (WCB No. 21/004), the Newcastle & North Tyneside 2 Research Ethics Committee (IRAS ID: 294246) and Cardiff University School of Medicine Research Ethics Committee (SREC reference: SMREC 21/01).
    Consent: All participants gave written, informed consent prior to inclusion.
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    Detection of anti-SARS-CoV-2 RBD IgG Antibodies: An in-house direct ELISA was developed as previously described (16-19), with some modifications.
    anti-SARS-CoV-2 RBD IgG
    suggested: None
    Wells were washed three times with PBS-T then incubated (1 hour, room temperature) with secondary antibody (donkey anti-human IgG F(ab’)2-horseradish peroxidase (HRP); #709-036-149, Jackson ImmunoResearch, Ely, UK) for 1 hour at room temperature.
    anti-human IgG
    suggested: (Jackson ImmunoResearch Labs Cat# 709-036-149, RRID:AB_2340498)
    Software and Algorithms
    SentencesResources
    IFN-γ was quantified by extrapolating from the standard curve using Graphpad Prism.
    Graphpad Prism
    suggested: (GraphPad Prism, RRID:SCR_002798)
    : GraphPad Prism Version 9 was used for all statistical analyses of datasets.
    GraphPad
    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

    SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore checks for the presence and correctness of RRIDs (research resource identifiers), and for rigor criteria such as sex and investigator blinding. For details on the theoretical underpinning of rigor criteria and the tools shown here, including references cited, please follow this link.

  3. Version published to 10.1101/2021.06.02.21258218v1 on medRxiv