The mechanism for maintenance of memory CD8 T Cells after COVID-19 mRNA vaccination 9160

Description During the SARS-CoV-2 pandemic, mRNA vaccines were administered globally. These vaccines induce strong antibody and CD4 T-cell responses, but CD8 T-cell responses vary among individuals and decrease quickly. This study explores mechanisms behind memory CD8 T-cell responses induced by the COVID-19 mRNA vaccine. Blood samples from 177 donors were collected at pre-vaccination, 2 weeks, and 6 months after 3rd dose of COVID-19 mRNA vaccine. A total of 142 donors with either HLA-A*24:02 or HLA-A*02:01 were analyzed for the spike-specific CD8 T-cell responses using HLA class I tetramers against CD8 T-cell epitopes, such as HLA-A*24:02-restricted NF9 (NYNYLYRLF), QI9 (QYIKWPWYI), and HLA-A*02:01-restricted YL9 (YLQPRTFLL). At 2 weeks post-boost, QI9-, NF9-, and YL9-specific CD8 T cells were detected in 33.7% (34 /101 donors), 19.8% (20 /101 donors), and 17.3% (14 /81 donors), respectively. However, 6 months post-boost, the frequency of these cells decreased. Besides, enhanced expression of Notch signaling pathway genes was observed in donors with maintained the spike-specific CD8 T cells. Furthermore, an in vitro stimulation assay of Spike epitope-specific CD8 T cells revealed that under Notch signal inhibition, the proliferation of QI9- and NF9-specific CD8 T cells was suppressed. Together, these findings suggest that Notch signal is crucial for the long-term maintenance of CD8 T-cell responses and enhancing this pathway could improve CD8 T-cell response induction by mRNA vaccines.