Clonal dynamics of SARS-CoV-2 specific CD4 T cells in lymph nodes after vaccination

Abstract

Abstract The ongoing COVID-19 pandemic highlight the importance of vaccination. Past studies have surveyed SARS-CoV-2 specific B cell response in the lymph node (LN) of vaccinated patient, but the quality, the dynamics, and the specificity of the T helper response following mRNA vaccination remains incompletely understood. We address this question in healthy individuals receiving mRNA vaccine (BNT162b or mRNA-1273). We collected axillary draining LN using fine needle aspiration following vaccination and analyzed CD4+ T cells by single cell transcriptome, proteome analysis and TCR sequencing. We observed an accumulation T cell having characteristic signature of activated T follicular helper cell (Tfh), through the course of the 6 months, as well as an increase expansion of Tfh clones. Using TCR sequences to track progenies of same T cell over time, we observed that some Tfh cells in the 6 months’ time point were already detectable after the first vaccine dose. We then generated a library of SARS-CoV-2 specific TCR sequences by performing TCR sequencing on cells that proliferated in response to a spike peptide pool. The majority of these TCR sequences mapped to cells with a strong Tfh signature on the transcriptomic level and accumulated after 6 months. In conclusion, we observed an expansion of SARS-CoV-2 specific Tfh clones after the first dose of vaccine, some of which persisted after 6 months. We hypothesize that, in a protective SARS-CoV-2 response, short-lived clones are progressively replaced by long-lasting SARS-CoV-2 specific Tfh clones. We plan to test this hypothesis by analyzing clonal dynamics at other time points and by using aggregate TCR sequences from the publicly available sequences from individuals with mild or severe COVID-19. NIH R01AO66358