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

mRNA vaccines against the Spike glycoprotein of severe acute respiratory syndrome type 2 coronavirus (SARS-CoV-2) elicit strong T-cell responses. However, it’s not known whether T cell clonotypes responding to the first vaccination repeatedly expand with booster vaccinations. Here, we temporally tracked the CD8+ T-cell repertoire in individuals who received three shots of the BNT162b2 mRNA vaccine. By analyzing the kinetic profile of CD8+ T-cell clonotypes responding to the first, second, or third shot, we demonstrated that newly expanded clonotypes elicited by the second shot replaced many of those that responded to the first shot. Although these 2nd responder clonotypes expanded after the third shot, their clonal diversity was skewed, and they were partially replaced by newly elicited the 3rd responders. Furthermore, this replacement of vaccine-responding clonotypes occurred within the same Spike epitope. These results suggest that CD8+ T-cell memory induced by repetitive mRNA vaccination is characterized by the emergence of new dominant clones. ### Competing Interest Statement H.A. reports stock for ImmunoGeneTeqs, Inc. S.S. reports advisory role for ImmunoGeneTeqs, Inc; stock for ImmunoGeneTeqs, Inc, T.I. reports research funding from Rohto Pharmaceutical Co., Ltd., and Biometrics Sympathies Inc. K.M. reports consulting or advisory role for Kyowa-Hakko Kirin, ImmunoGeneTeqs, Inc; research funding from Kyowa-Hakko Kirin, and Ono; stock for ImmunoGeneTeqs, Inc, IDAC Theranostics, Inc. S.U. reports advisory role for ImmunoGeneTeqs, Inc; stock for ImmunoGeneTeqs, Inc, IDAC Theranostics, Inc.