CD8+ T cell memory induced by successive SARS-CoV-2 mRNA vaccinations is characterized by shifts in clonal dominance

Abstract

mRNA vaccines against the spike glycoprotein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) elicit strong Tcell responses. However, a clonal-resolution analysis of Tcell responses to mRNA vaccination has not been performed. Here, we temporally track the CD8+ Tcell repertoire in individuals who received three shots of the BNT162b2 mRNA vaccine through longitudinal Tcell receptor sequencing with peptide-human leukocyte antigen (HLA) tetramer analysis. We demonstrate a shift in Tcell responses between the clonotypes with different kinetics: from early responders that expand rapidly after the first shot to main responders that greatly expand after the second shot. Although the main responders re-expand after the third shot, their clonal diversity is skewed, and newly elicited third responders partially replace them. Furthermore, this shift in clonal dominance occurs not only between, but also within, clonotypes specific for spike epitopes. Our study will be a valuable resource for understanding vaccine-induced Tcell responses in general.