Vaccine-induced T cell responses correlate with reduced risk of severe COVID-19 in a placebo-controlled efficacy trial

作者：Nina Hertoghs, Sanne Roels, Matthias Brückner, Jerald Sadoff, Barbara L. Banbury, Nicholas K. Akers, Bryan Howie, Harlan Robins, Griet A. Van Roey, Jeroen Tolboom, Veronica V. Rezelj, Jenny Hendriks, Hanneke Schuitemaker, Daniel J Stieh, Mathieu Le Gars · 发表于：EBioMedicine · 年份：2025 · DOI：10.1016/j.ebiom.2025.105809 · 被引用次数：9 · 研究领域：SARS-CoV-2 and COVID-19 Research、COVID-19 Clinical Research Studies、Immune responses and vaccinations

BACKGROUND: While vaccine-induced SARS-CoV-2 antibodies provide partial protection against COVID-19, a significant question remains regarding the role of vaccine-induced T cells in combating COVID-19. The purpose of this study is to investigate whether signatures of the T-cell response contribute to protection against (severe) COVID-19. METHODS: T cell receptor (TCR) sequencing was conducted using pre-vaccination and 29 days post-vaccination PAXgene samples from 396 participants in the phase 3 efficacy trial, ENSEMBLE. The dataset consists of 198 individuals who developed breakthrough COVID-19 infections, including 23 severe cases, and an equal number of matched control subjects. Immunosequencing and subsequent computational analysis was performed to identify SARS-CoV-2 and Spike-specific TCRs to quantify SARS-CoV-2 specific T cell breadth, depth, clonal expansion, and a model test score that describes magnitude of cellular response compared to pre-pandemic controls. FINDINGS: Preliminary analyses demonstrated high concordance and correlation between functional T cell responses measured by a standard intracellular cytokine staining and TCR sequencing metrics. Furthermore, vaccine-elicited T cell responses correlated inversely with the risk of developing severe COVID-19, while no strong relation was observed with overall symptomatic COVID-19 risk. A multivariable analysis including neutralizing antibody data and TCR scores indicated that, in addition to humoural responses, T c...