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

Abstract

Memory CD8 Tcells 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 Tcell response against a common SARS-CoV-2 epitope after vaccination, infection, or both. CD8 Tcells demonstrate comparable functional capacity when restimulated directly exvivo, independent of the antigenic history. However, analysis of Tcell receptor usage shows that vaccination results in a narrower scope than infection alone or in combination with vaccination. Importantly, in an invivo recall model, memory CD8 Tcells 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.