Interleukin-2: an accurate biomarker for rapid testing of SARS-CoV-2 vaccine-induced T cell immune responses in whole blood

Background: T cell responses to natural SARS-CoV-2 infection may be more robust and longer lived than antibody responses, thus preventing re-infection. Accurate assessment of vaccine-induced T cell responses is critical for understanding the magnitude and longevity of vaccine-induced immunity across patient cohorts. Aims: To establish a simple, accurate and rapid whole blood test to determine natural and vaccine-induced SARS-CoV-2 immunity via a cytokine release assay. Methods: Cytokine release in whole blood stimulated with peptides specific for SARS-CoV-2 was measured in donors with PCR-confirmed previous infection (n=29), suspected infection (n=30) or with no history of exposure (n=69); and in donors pre- and post-vaccination (n=32). Cytokines were measured by enzyme immunoassay and multiplex array. Results: Cytokines interleukin-2 (IL-2) and interferon-gamma (IFN-γ) were highly elevated in PCR-confirmed or suspected SARS-CoV-2 infected donors at 20->2000pg/ml and 20-1000pg/ml, respectively, compared to history negative controls (<20-90pg/ml). Receiver operating curves showed IL-2 as the superior biomarker with AUC of 0.99 compared to IFN-γ (0.94). Following vaccination, 100% of PCR-confirmed donors and 94% of unexposed individuals demonstrated a positive IL-2 response. Mean IL-2 levels increased ~18-fold from 12pg/ml pre-vaccination to 202pg/ml and 216pg/ml after the 1 and 2 vaccine doses, respectively. No other cytokines were suitable biomarkers for distinguishing SARS-CoV-2 infection or vaccination responses. Conclusion: This rapid, whole blood-based T cell test can be utilised to make accurate and comparable assessments of vaccine-induced T cell immunity across multiple population cohorts, and aid decision making on public health policies and vaccine efficacy.