Booster mRNA vaccination post-SARS-CoV-2 infection enhances functional qualities of T cell immunity

Abstract T cells are critical to generate protection from severe respiratory viral disease. Whether repeated SARS-CoV-2 antigen exposure through vaccination causes cell exhaustion or gain of functions remains debated. In this study, we sampled convalescent donors before and after determine the functional consequences hybrid immunity. Donors were at 6 months 18 convalescence divided according their history mild severe/hospitalized disease (n = 44 45 respectively). between two sampling timepoints, also received mRNA national COVID-19 program. Using activation-induced marker assays, intracellular cytokine staining, single-cell transcriptomics T-cell receptor sequencing analyses, show that spike-specific increase in magnitude but, importantly, highly characteristics. By contrast, responses non-spike proteins diminished remained unchanged. Elevated interferon-gamma expression was a common hallmark CD4+ CD8+ post-mRNA-vaccination. These founded on both pre-expanded newly detected clones vaccination. Collectively, these data demonstrate cumulative benefits booster vaccinations, leading increased quantity quality cell-mediated Supported by grant Karolinska Institutet Research foundation grants (2022-01708)