Here, using nontransgenic immunocompetent C57BL/6 mice, we have systematically analyzed the kinetics, phenotype, and tissue distribution of COVID-19 human mRNA vaccine–elicited antigen-specific CD8 T cells as well as the role of memory CD4 and CD8 T cells in controlling SARS-CoV-2 replication in the lungs. Here, CD4 is linked to COVID-19.