Longitudinal analysis of antigen-specific T cells after Shingrix vaccination
SHINGRIX vaccination was used to investigate the fate of antigen specific memory CD4+ T cell at both cellular and transcriptional level upon immunization in a one-year longitudinal study. SHINGRIX is a subunit vaccine with glycoprotein E (gE) of varicella zoster virus (VZV) as the immunogen and requires two doses at least 60 days apart for protection against Herpes Zoster in adults over 50 years old. Flow cytometry and single-cell RNA sequencing were used to evaluate cellular and transcriptomic changes of VZV gE epitope-specific CD4+ T cells in a TCR clonotypic fashion pre and post vaccination. Antigen-specific T cells remained at a higher frequency compared to baseline and retained markers of cell activation such as ICOS and PD1 even one year post-vaccination. Persistent TCR clonotypes amongst epitope-specific T-cells were common across different time points within each individual. Antigen-specific memory T cells with a dominant TCR clonotype at baseline remained at a relatively high frequency one year later after two doses of vaccine. In contrast, T cells with TCR clonotypes from naïve antigen specific cells at baseline could not be detected post-vaccination. Differential gene expression analyses of cells with identical TCR clonotypes show that cells post vaccination, including those at one year post vaccination, were distinct from cells at baseline, with upregulation of genes related to T cell differentiation, negative T cell regulation and T cell activation. Thus, in addition to an increase in frequency, committed memory T cells gain additional transcriptional changes upon vaccination that could alter the immune response against cognate immunogens compared to pre-vaccinated quiescent memory T cells. Overall design: Varicella-Zoster virus  glycoprotein E-specific CD4 T Cells were sorted from blood from 7 patients treated with the Shingrix vaccine in two doses at days 0, 60, 74, and 365. Flow cytometry and single-cell RNA-Seq measured surface protein markers and RNA expression of these cells. TCR sequences were assembled from the RNA-Seq data.