Abstract
The emergence of SARS-CoV-2 variants during the COVID-19 pandemic prompted updates to the original vaccines to improve immunogenicity against novel SARS-CoV-2 variants. Since 2022, vaccination guidelines introduced updated mRNA boosters, starting with a bivalent formulation that included the original and Omicron BA.4/BA.5 spike sequences, which emerged in late 2021. In this study, we characterized the spike-specific T cell response following the bivalent booster vaccination in humans. We performed an in-depth profiling of T cells, assessing activation markers, cytokine production and the impact of previous COVID-19 infection in the response to different spike variants. Overall, our results are consistent with the bivalent booster having a limited influence on spike-T cell responses, with similar magnitude and functionality observed toward the Omicron BA.4/BA.5 variant and the ancestral spike. Nonetheless, the booster proved to be beneficial for immunocompetent individuals with poor or declining T cell responses, increasing the frequency of specific T cells in blood.