Introduction:
To date, there have been more than 200,757,931 COVID-19 cases and 4,266,367 deaths documented world-wide1. This has led to massive human suffering and disruption of global economies. The limited efficacy of most treatments and high death rates have focused on vaccines as the last best hope for stemming the pandemic. In general, this has been true2. However, the persistence of the SARS-CoV-2 epidemic, driven primarily by variants of concern (VOC), have raised concerns that this will pose potential challenges to our ability to provide effective sterilizing and durable immunity through vaccination3. This brings into question whether the composition of SARS-CoV-2 immunity garnered by previous infection or vaccination could respond effectively to emerging VOC or would require constant re-vaccination with an ever-changing composition of viral mRNAs or peptides to meet the potential pathogenic threat.
Since the advent of the epidemic, attempts to define the composition and duration of immune responses in infected and, more recently, vaccinated individuals have been ardently pursued4,5. Important early advances were achieved in describing antibody responses after infection, but concerns arose regarding the rapid and unpredictable dissipation of IgG responses to SARS-CoV-2 peptides and the potential effect on long-term immunity5-7. In addition, reports have shown that IgG spike protein immune responses to the BNT162b2 (Pfizer) vaccine may have reduced activity against the United Kingdom (UK, B.1.1.7) variant8.
A better understanding of this important issue would benefit from analysis of CD4+/CD8+ T-cell responses to SARS-CoV-2 spike peptides and variants9-11. SARS-CoV-2-specific T-cell immunity was detected in COVID-19 patients as well as uninfected healthy controls9,10. Early and/or robust T-cell immunity has been associated with rapid viral clearance and mild symptoms in COVID-19 patients11,12. Thus, an analysis of T-cell reactivity to SARS-CoV-2 and VOC would aid in our understanding of the breadth and depth of human immune responses after infection and vaccination.
Here we report on the development of a sensitive whole blood assay to detect CD4+/CD8+ T-cell cytokine responses to SARS-CoV-2 and variant peptides. This information could be helpful in understanding the composition and durability of human immunity to SARS-CoV-2 and a VOC.