Abstract
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 1st and
2nd 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.