The High Expression of PD-1 Defines A Subpopulation of Tfh Cells Responding to COVID-19 Vaccine in Humans

Abstract Inactivated coronavirus disease 2019 (COVID-19) vaccines and receptor binding domain subunit (RBD-subunit) booster vaccination can induce effective humoral immune response. CD4+ T helper cells are essential in helping B cells and antibody response. However, the response of CD4+ T cells to booster vaccination, especially the virus-induced T follicular helper (Tfh) cells, needs to be better characterized. In this study, it was investigated using tools of single-cell sequencing and flow cytometry. Additionally, a customized analysis algorithm was applied to identify virus-induced T cell receptor (VI-TCR) which is useful to explore the activation and persistence of virus-induced CD4+ T cell response. We identified a subset of classic Tfh (cTfh) cells with high expression of PD-1 and IFN-γ. They were notably activated following booster vaccination, and their proportion was correlated with the antibody titer level. We used trajectory analysis to analyze the dynamic changes of activated and found that a subset of virus-induced cTfh cells might maintain immune responses beyond 90 days post-vaccination. In summary, we found a group of PD-1high cTfh cells in COVID-19 vaccination, which can enhance the humoral response and show the persistence of immune response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We also provided a method for single-cell immune data analysis to understand the virus-induced responses. Understanding how cTfh cells help antibody production will provide essential insights into the rational design of new vaccine strategies to optimize long-term immunity.