@article{10.1172/jci.insight.154187, author = {Hannah R. Sharpe AND Nicholas M. Provine AND Georgina S. Bowyer AND Pedro Moreira Folegatti AND Sandra Belij-Rammerstorfer AND Amy Flaxman AND Rebecca Makinson AND Adrian V.S. Hill AND Katie J. Ewer AND Andrew J. Pollard AND Paul Klenerman AND Sarah Gilbert AND Teresa Lambe}, journal = {JCI Insight}, publisher = {The American Society for Clinical Investigation}, title = {CMV-associated T cell and NK cell terminal differentiation does not affect immunogenicity of ChAdOx1 vaccination}, year = {2022}, month = {3}, volume = {7}, url = {https://insight.jci.org/articles/view/154187}, abstract = {Cytomegalovirus (CMV) is a globally ubiquitous pathogen with a seroprevalence of approximately 50% in the United Kingdom. CMV infection induces expansion of immunosenescent T cell and NK cell populations, with these cells demonstrating lower responsiveness to activation and reduced functionality upon infection and vaccination. In this study, we found that CMV+ participants had normal T cell responses after a single-dose or homologous vaccination with the viral vector chimpanzee adenovirus developed by the University of Oxford (ChAdOx1). CMV seropositivity was associated with reduced induction of IFN-γ–secreting T cells in a ChAd-Modified Vaccinia Ankara (ChAd-MVA) viral vector vaccination trial. Analysis of participants receiving a single dose of ChAdOx1 demonstrated that T cells from CMV+ donors had 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 after vaccination. NK cells from CMV-seropositive individuals also had 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, which has important implications given the widespread use of this vaccine, particularly in low- and middle-income countries with high CMV seroprevalence.}, number = {6}, doi = {10.1172/jci.insight.154187}, url = {https://doi.org/10.1172/jci.insight.154187}, }