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
st and 2 nd 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.