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.