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

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 upo...

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Detalles Bibliográficos
Autores principales: Sharpe, Hannah R., Provine, Nicholas M., Bowyer, Georgina S., Moreira Folegatti, Pedro, Belij-Rammerstorfer, Sandra, Flaxman, Amy, Makinson, Rebecca, Hill, Adrian V.S., Ewer, Katie J., Pollard, Andrew J., Klenerman, Paul, Gilbert, Sarah, Lambe, Teresa
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Clinical Investigation 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8986084/
https://www.ncbi.nlm.nih.gov/pubmed/35192547
http://dx.doi.org/10.1172/jci.insight.154187
Descripción
Sumario: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.