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 ORCID: https://orcid.org/0000-0002-4120-0688, Zelek, Wioleta, Lippiatt, George, Somerville, Michelle, Burnell, Stephanie, 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 ORCID: https://orcid.org/0000-0002-5166-9236, Morgan, Bryan Paul ORCID: https://orcid.org/0000-0003-4075-7676, Gallimore, Awen ORCID: https://orcid.org/0000-0001-6675-7004 and Godkin, Andrew ORCID: https://orcid.org/0000-0002-1910-7567 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) , pp. 250-259. 10.1111/imm.13433

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Abstract

Accurate assessment of SARS-CoV-2 immunity is critical to 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 optimised 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 to 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 116/128 (90.6%) of healthy donors, reducing significantly to 27/56 (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 standardisable 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.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine Pharmacy
Additional Information:	This is an open access article under the terms of the Creative Commons Attribution License
Publisher:	Wiley
ISSN:	0019-2805
Funders:	Wellcome Trust, Cancer Research UK
Date of First Compliant Deposit:	11 November 2021
Date of Acceptance:	17 September 2021
Last Modified:	23 Jan 2025 22:30
URI:	https://orca.cardiff.ac.uk/id/eprint/145428

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