Ablation of CD8+ T-cell recognition of an immunodominant epitope in SARS-CoV-2 Omicron

The emergence of the SARS-CoV-2 Omicron variant has raised concerns of escape from vaccine-induced immunity. A number of studies have demonstrated a reduction in antibody-mediated neutralization of the Omicron variant in vaccinated individuals. Preliminary observations have suggested that T cells are less likely to be affected by changes in Omicron. However, the complexity of human leukocyte antigen genetics and its impact upon immunodominant T-cell epitope selection suggests that the maintenance of T-cell immunity won’t be universal. In this study, we describe the impact that changes in Omicron have on recognition by spike-specific T cells. These T cells constitute the immunodominant CD8+ T-cell response in HLA-A*29:02+ COVID-19 convalescent and vaccinated individuals; however, they fail to recognize the Omicron-encoded sequence. We also failed to detect other immunodominant responses in vaccinated HLA-A*29:02+ individuals, suggesting that the Omicron variant may have an increased capacity to escape immune recognition in this population.