Understanding the landscape of the SARS-CoV-2-specific T cells post-omicron surge

Emerging evidence shows increased humoral response post-omicron surge, but research on T cell responses is limited. This study investigated the durability, magnitude, and breadth of SARS-CoV-2-spike-specific T cell responses in 216 two-dose vaccinated individuals pre- and post-omicron surge. Post-surge samples showed enhanced T cell responses, indicating widespread asymptomatic exposure to omicron. Further analysis of 105 individuals with multiple exposures to SARS-CoV-2 through boosters or infections showed that post-omicron, two-dose vaccinated individuals had T cell responses comparable to those of COVID-19 convalescents or boosted individuals. Additionally, we report cross-reactive T cell responses against omicron sub-variants, including BA2.86, remained strong, with preserved frequencies of spike-specific stem-cell-like memory T cells. In silico prediction indicates that mutated epitopes of JN.1 and KP.2 retain over 95.6% of their HLA binding capability. Overall, our data suggests that T cell responses are sustained, enhanced, and cross-reactive against emerging SARS-CoV-2 variants following symptomatic or asymptomatic omicron infection.