Longitudinal single cell profiling of epitope specific memory CD4+ T cell responses to recombinant zoster vaccine

Xiaomin Wen, Alex K. Hu, Scott R. Presnell, Emily S. Ford, David M. Koelle and William W. Kwok ()
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Xiaomin Wen: Benaroya Research Institute at Virginia Mason
Alex K. Hu: Benaroya Research Institute at Virginia Mason
Scott R. Presnell: Benaroya Research Institute at Virginia Mason
Emily S. Ford: University of Washington School of Medicine
David M. Koelle: Benaroya Research Institute at Virginia Mason
William W. Kwok: Benaroya Research Institute at Virginia Mason

Nature Communications, 2025, vol. 16, issue 1, 1-16

Abstract: Abstract Vaccination leads to rapid expansion of antigen-specific T cells within in the first few days. However, understanding of transcriptomic changes and fates of antigen-specific T cells upon vaccination remains limited. Here, we investigate the fate of memory CD4+ T cells upon reactivation to recombinant zoster vaccine for shingles at cellular and transcriptional levels. We show that glycoprotein E-specific memory CD4+ T cells respond strongly, their frequencies remain high, and they retain markers of cell activation one year following vaccination. Memory T cells with the most dominant TCR clonotype pre-vaccination remain prevalent at year one post-vaccination. These data implicate a major role for pre-existing memory T cells in perpetuating immune repertoires upon re-encountering cognate antigens. Differential gene expression indicates that cells post-vaccination are distinct from cells at baseline, suggesting committed memory T cells display transcriptional changes upon vaccination that could alter their responses against cognate immunogens.

Date: 2025
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DOI: 10.1038/s41467-025-57562-7

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