Vaccination provides superior in vivo recall capacity of SARS-CoV-2-specific memory CD8 T cells

Memory CD8 T cells play an important role in the protection against breakthrough infections with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Whether the route of antigen exposure impacts these cells at a functional level is incompletely characterized. Here, we compare the memory CD8 T cell response against a common SARS-CoV-2 epitope after vaccination, infection, or both. CD8 T cells demon-strate comparable functional capacity when restimulated directly ex vivo, independent of the antigenic his-tory. However, analysis of T cell receptor usage shows that vaccination results in a narrower scope than infection alone or in combination with vaccination. Importantly, in an in vivo recall model, memory CD8 T cells from infected individuals show equal proliferation but secrete less tumor necrosis factor (TNF) compared with those from vaccinated people. This difference is negated when infected individuals have also been vaccinated. Our findings shed more light on the differences in susceptibility to re-infection after different routes of SARS-CoV-2 antigen exposure.

Automated summary

Memory CD8 T cells play an important role in protection against breakthrough infections with SARS-CoV-2. The route of antigen exposure impacts the functional capacity of these cells. Vaccination results in a narrower T cell receptor usage scope compared to infection alone or in combination with vaccination. Infected individuals with memory CD8 T cells secrete less TNF compared to vaccinated individuals, but this difference is negated if infected individuals have also been vaccinated. Our findings provide insights into susceptibility to re-infection after different routes of SARS-CoV-2 antigen exposure.