CMV-associated T cell and NK cell terminal differentiation does not affect immunogenicity of ChAdOx1 vaccination.
Sharpe, Hannah R
Provine, Nicholas M
Moreira Folegatti, Pedro
Hill, Adrian Vs
Ewer, Katie J
Pollard, Andrew J
American Society for Clinical Investigation
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Sharpe, H. R., Provine, N. M., Bowyer, G., Moreira Folegatti, P., Belij-Rammerstorfer, S., Flaxman, A., Makinson, R., et al. (2022). CMV-associated T cell and NK cell terminal differentiation does not affect immunogenicity of ChAdOx1 vaccination.. JCI Insight, 7 (6. ARTN e154187) https://doi.org/10.1172/jci.insight.154187
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.
COVID-19, NK cells, T cells, Vaccines, ChAdOx1 nCoV-19, Cytomegalovirus, Cytomegalovirus Infections, Humans, Killer Cells, Natural, Seroepidemiologic Studies, Vaccination
External DOI: https://doi.org/10.1172/jci.insight.154187
This record's URL: https://www.repository.cam.ac.uk/handle/1810/336594
Attribution 4.0 International
Licence URL: https://creativecommons.org/licenses/by/4.0/