CMV-associated T cell and NK cell terminal differentiation does not affect immunogenicity of ChAdOx1 vaccination
Sharpe HR., Provine NM., Bowyer GS., Moreira Folegatti P., Belij-Rammerstorfer S., Flaxman A., Makinson R., Hill AVS., Ewer KJ., Pollard AJ., Klenerman P., Gilbert S., Lambe T.
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.