Epitope-specific T cell responses after SARS-2 vaccination, including for a hypervaccinated individual

Prime-boost vaccinations tailor adaptive immunity. However, chronic antigen exposure can also lead to immune dysfunction. Overall, the benefits and limits of repetitive antigen exposure for vaccinations in humans remain poorly understood. Here we performed in-depth immune profiling in an individual that reports 217 vaccinations (including 134 certified doses) against SARS-CoV-2 in less than two years (Hypervaccinated Individual from Magdeburg, HIM). Antigen-specific antibody and T-cell responses were of higher quantity, while quality was preserved, compared to a three-dose mRNA vaccine control cohort. Hyperimmunization did not lead to adverse events and HIM remains SARS-CoV-2 infection-free. Insights from extreme settings like the one reported here instruct our understanding on the consequences of repetitive antigen exposure on adaptive immunity in humans. Overall design: Antigen-specific T cells (as well as unspecific T cells as a control) were identified by DNA-baroded pMHC multimers (Dextramers) including the SARS-CoV-2 specificity LTD as well as the EBV specificity RAK. Dextramer+ and - cells were sorted by FACS and subjected to 5' scRNAseq on a 10x Genomics platform including CITEseq for Dextramers and, for some samples, 130 surface proteins; different samples from different donors were labelled with hasthag antibodies