Evolution of SARS-CoV-2 T cell responses as a function of multiple COVID-19 boosters
Ricardo da Silva Antunes, Vicente Fajardo-Rosas, Esther Dawen Yu, Rosa Isela Gálvez, Adam Abawi, E. Alexandar Escarrega, Amparo Martínez-Pérez, Emil Johansson, Benjamin Goodwin, April Frazier, Jennifer M. Dan, Shane Crotty, Grégory Seumois, Daniela Weiskopf, Pandurangan Vijayanand, Alessandro Sette
Abstract
We investigate the long-term impact of repeated COVID-19 vaccinations on adaptive immunity through a 3-year study of 78 individuals without reported symptomatic infections. We observe distinct dynamics in spike-specific responses across multiple vaccine doses. While antibody levels increase and stabilize with each booster, T cell responses quickly plateau and remain stable. Notably, approximately 30% of participants show evidence suggestive of asymptomatic infections. Single-cell RNA sequencing reveals a diverse and stable landscape of spike-specific T cell phenotypes without signs of exhaustion or functional impairment. Individuals with evidence of asymptomatic infection display increased frequencies of Th17-like CD4 + T cells and GZMKhi/IFNR + CD8 + T cell subsets. In this group, repeated vaccinations correlate with an increase in regulatory T cells, potentially indicating a balanced immune response that may mitigate immunopathology. By regularly stimulating T cell memory, boosters contribute to a stable and enhanced immune response, which may provide better protection against symptomatic infections.