Whole blood-based measurement of SARS-CoV-2-specific T cell responses reveals asymptomatic infection and vaccine efficacy in healthy subjects and patients with solid organ cancers

This research has not been peer-reviewed. It is a preliminary report that should not be regarded as conclusive, guide clinical practice or health-related behaviour, or be reported in news media as established information.

Accurate assessment of SARS-CoV-2 immunity in the population 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 of the immune response 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 156 healthy donors and 67 cancer patients. Following overnight in vitro stimulation with SARS-CoV-2-specific peptides, blood plasma samples were harvested and analysed for TH1-type effector cytokines (IFN-γ and IL-2). Amongst healthy donors, highly significant differential IFN-γ+/IL-2+ SARS-CoV-2-specific T cell responses were seen amongst vaccinated or previously infected COVID-19-positive individuals in comparison to unknown/naïve individuals (P < 0.0001). IL-2 production from T cells in response to SARS-CoV-2 derived antigens was a highly predictive diagnostic assay (P < 0.0001; 96.0% sensitivity, 93.9% specificity); measurement of IFN-γ+ SARS-CoV-2 specific T cell responses was equally effective at identifying asymptomatic (antibody and T cell positive) participants. A single dose of COVID-19 vaccine induced IFN-γ and/or IL-2 SARS-CoV-2-specific T cell responses in 28/29 (96.6%) of healthy donors, reducing significantly to 27/56 (48.2%) when measured in cancer patients (P = 0.0003). 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.

Author list

Martin J. Scurr1,2, Wioleta M. Zelek3,4, George Lippiatt2, Michelle Somerville1, Stephanie E. A. Burnell1, Lorenzo Capitani1, Kate Davies5, Helen Lawton5, Thomas Tozer6, Tara Rees6, Kerry Roberts6, Mererid Evans7, Amanda Jackson7, Charlotte Young7, Lucy Fairclough8, Mark Wills9, Andrew D. Westwell10, B. Paul Morgan3,4, Awen Gallimore*1,3§ and Andrew Godkin*1,3,6§

1 Division of Infection & Immunity, School of Medicine, Cardiff University, Cardiff, UK.
2 ImmunoServ Ltd., Cardiff, UK
3 Systems Immunity University Research Institute, School of Medicine, Cardiff University, Cardiff, UK. 4 UK Dementia Research Institute Cardiff, Cardiff University, Cardiff, UK.
5 Radyr Medical Centre, Cardiff, UK.
6 Dept. of Gastroenterology & Hepatology, University Hospital of Wales, Heath Park, Cardiff, UK.
7 Velindre Cancer Centre, Cardiff, UK.
8 School of Life Sciences, University of Nottingham, Nottingham, UK.
9 Department of Medicine, Addenbrookes Hospital, University of Cambridge, Cambridge, UK.
10 School of Pharmacy and Pharmaceutical Sciences, Cardiff University, Cardiff, UK.

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