Personalized HLA-aware TCR measure predicts the risk of symptomatic SARS-CoV-2 infection following booster vaccination

HLA-driven heterogeneity and limitations of live T cell functional assays routinely thwart assessment of cell-mediated immunity in vaccination trials. To address this, we developed a T-cell receptor (TCR)-based measure of immunogen recognition and evaluated it in COV-BOOST, a third-dose COVID-19 vaccine trial, during the Delta and Omicron waves (2021-2022, United Kingdom). We estimated HLA-aware Spike-reactive T cell (HA-TS) breadth from participant HLA genotypes, TCR{beta} repertoires, and a novel SARS-CoV-2 S HLA-linked reference catalog. Higher post-boost HA-TS breadth was associated with l

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