...In this study, we found that CMV+ participants had normal T cell responses after single dose or homologous vaccination with the viral vector ChAdOx1. In contrast, CMV seropositivity was associated with a loss of T cell IFN-γ secretion following heterologous ChAd-MVA viral vector vaccination. Analysis of participants receiving a single dose of ChAdOx1 demonstrates that T cells from CMV+ donors have a more terminally differentiated profile of CD57+PD1+ CD4+ T cells and CD8+ T cells expressing less IL-2Rα (CD25), and fewer polyfunctional CD4+ T cells 14 days post-vaccination. NK cells from CMV-seropositive individuals also have a reduced activation profile. Overall, our data suggest that although CMV infection enhances immunosenescence of T and NK populations, it does not affect antigen-specific T cell IFN-γ secretion or antibody IgG production after vaccination with the current ChAdOx1 nCoV-19 vaccination regimen in the UK.