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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

Scurr, Martin J.; Zelek, Wioleta M.; Lippiatt, George; Somerville, Michelle; Burnell, Stephanie E.A.; Capitani, Lorenzo; Davies, Kate; Lawton, Helen; Tozer, Thomas; Rees, Tara; Roberts, Kerry; Evans, Mererid; Jackson, Amanda; Young, Charlotte; Fairclough, Lucy; Tighe, Paddy; Wills, Mark; Westwell, Andrew D.; Morgan, B. Paul; Gallimore, Awen; Godkin, Andrew

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 Thumbnail


Authors

Martin J. Scurr

Wioleta M. Zelek

George Lippiatt

Michelle Somerville

Stephanie E.A. Burnell

Lorenzo Capitani

Kate Davies

Helen Lawton

Thomas Tozer

Tara Rees

Kerry Roberts

Mererid Evans

Amanda Jackson

Charlotte Young

PATRICK TIGHE paddy.tighe@nottingham.ac.uk
Professor of Molecular Immunology

Mark Wills

Andrew D. Westwell

B. Paul Morgan

Awen Gallimore

Andrew Godkin



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 TH1-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.

Citation

Scurr, M. J., Zelek, W. M., Lippiatt, G., Somerville, M., Burnell, S. E., Capitani, L., …Godkin, A. (2022). 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. Immunology, 165(2), 250-259. https://doi.org/10.1111/imm.13433

Journal Article Type Article
Acceptance Date Nov 3, 2021
Online Publication Date Dec 6, 2021
Publication Date 2022-02
Deposit Date Jan 31, 2022
Publicly Available Date Jan 31, 2022
Journal Immunology
Print ISSN 0019-2805
Electronic ISSN 1365-2567
Publisher Wiley
Peer Reviewed Peer Reviewed
Volume 165
Issue 2
Pages 250-259
DOI https://doi.org/10.1111/imm.13433
Keywords Immunology; Immunology and Allergy
Public URL https://nottingham-repository.worktribe.com/output/7024070
Publisher URL https://onlinelibrary.wiley.com/doi/10.1111/imm.13433

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