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

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; Wills, Mark; Westwell, Andrew D.; Morgan, B. Paul; Gallimore, Awen; Godkin, Andrew

Abstract

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.

• Deposit Date: Jun 9, 2021
• Publicly Available Date: Jun 10, 2021
• Public URL: https://nottingham-repository.worktribe.com/output/5633663
• Publisher URL: https://www.medrxiv.org/content/10.1101/2021.06.02.21258218v1