Discussion
Simple, rapid and functional assays that accurately detect SARS-CoV-2-specific T cell responses are essential for comparing T cell immunity across multiple population cohorts and for long-term assessments of vaccine efficacy. The results show that measuring plasma IL-2 from SARS-CoV-2 peptide-stimulated whole blood accurately distinguishes between COVID-19 convalescents and uninfected healthy blood donors with a high degree of sensitivity and specificity. Plasma IL-2 was also an excellent biomarker for distinguishing vaccinated and unvaccinated individuals. Furthermore, T cell responses in previously unexposed individuals developed early after just one vaccination, were maintained after a second dose and were comparable to those with a history of SARS-CoV-2 infection; a finding that was not observed using ELISpot 18, 19. Positive IL-2 responses were still detectable up to 78 days post-vaccination, in keeping with observations that T cell responses are robust; in SARS-CoV-1 and MERS-CoV infected individuals, T cell responses were still identifiable several years after infection 20-22.
Reliable biomarkers are integral to assessing vaccine efficiency over time. Unlike other immunoassays that detect antigen-specific T cell responses such as ELISPOT and flow cytometry, this virus-specific IL-2 release assay is simple to perform and can be employed across multiple laboratories for large scale epidemiological studies in conjunction with testing for neutralising antibodies 23. The IL-2 release assay is a promising tool for use in multi-centre clinical trials for the development of new vaccines or treatments against novel SARS-CoV-2 variants, such as the delta variant, as they arise globally. Further studies of this approach should aid decision making by health policy makers, including vaccine booster requirements and monitoring of SARS-CoV-2 infection in immune-supressed and other at-risk populations.