CMV-associated T cell and NK cell terminal differentiation does not affect immunogenicity of ChAdOx1 vaccination.

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.

• Authors: Hannah R Sharpe, Nicholas M Provine, Georgina S Bowyer, Pedro Moreira Folegatti, Sandra Belij-Rammerstorfer, Amy Flaxman, Rebecca Makinson, Adrian Vs Hill, Katie J Ewer, Andrew J Pollard, Paul Klenerman, Sarah Gilbert, Teresa Lambe
• Journal: JCI insight (JCI Insight) Vol. 7 Issue 6 (03 22 2022) ISSN: 2379-3708 [Electronic] United States
• PMID: 35192547 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• ChAdOx1 nCoV-19

Topics

• ChAdOx1 nCoV-19
• Cytomegalovirus
• Cytomegalovirus Infections
• Humans
• Killer Cells, Natural
• Seroepidemiologic Studies
• Vaccination