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

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.

COVID‐19 Vaccine Response in People with Multiple Sclerosis

“… b A positive SARS‐CoV‐2‐specific T cell response was defined as an IFN‐gamma response >23.55 pg/ml and 50% above the negative (unstimulated) control value, as previously determined 5 …”

“…T cell responses to SARS‐CoV‐2 in 16 participants with negative humoral response to SARS‐CoV‐2 were measured using a commercially available whole blood assay (ImmunoServ Ltd.), as previously described. 5 Briefly, 10 ml venous blood from each patient was collected into sodium heparin vacutainers (BD) and processed in the laboratory within 6 hours of blood draw.…”

“…Plasma was harvested from the top of each blood sample the amount of IFN‐γ in each sample quantified. A previously defined positive SARS‐CoV‐2‐specific T cell response has a cutoff value of >23.55 pg/ml IFN‐γ and 50% above the negative (unstimulated) control value, differentiating naïve controls from prior COVID‐19 vaccination and/or previously infected subjects (sensitivity of 93.6% and specificity of 80.8%) 5 …”

“…a Time in months from the commencement of named DMT to the date of first COVID-19 vaccination. b A positive SARS-CoV-2-specific T cell response was defined as an IFN-gamma response >23.55 pg/ml and 50% above the negative (unstimulated) control value, as previously determined 5. COVID-19 = coronavirus disease 2019; DMT = disease modifying therapy; SARS-CoV-2 = severe acute respiratory syndrome-coronavirus 2. regardless…”

Retrospective diagnosis of SARS-CoV-2 infection in patients with Long COVID by measuring specific T cell mediated IL-2 release.

“…Interleukin-2 (IL-2) and Interferon (IFN)-g CD4 + and CD8 + T cell responses speci c to SARS-CoV-2 spike (S), nucleocapsid (N) and membrane (M) peptides are detected in PCR-positive individuals up to 12 months after infection, including in those who are seronegative [15,[23][24][25][26][27][28][29][30].…”