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This study examined immune responses in 60 older adults receiving high-dose influenza vaccination to understand why over one-third fail to respond adequately. Researchers found that strong responders showed a distinct immune signature involving early activation of dendritic cells and subsequent expansion of specific helper T cell populations, particularly influenza-specific Th10 cells that produce IL-10, while weak responders expanded regulatory T cells that may suppress immune responses. The Th10 cells were shown to promote B cell maturation into antibody-producing plasmablasts, representing a previously unrecognized mechanism supporting vaccine-induced antibody production.
Why it matters
Identifying the cellular mechanisms that distinguish strong from weak vaccine responses in older adults could enable development of strategies to improve vaccine effectiveness in this vulnerable population. The discovery of Th10 cells as key contributors to antibody responses may provide new targets for enhancing vaccine efficacy or predicting individual vaccine responsiveness.
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⚠️ Preprint – Noch nicht peer-reviewed
Dieser Artikel wurde noch nicht von unabhängigen Experten begutachtet. Die Ergebnisse sind vorläufig und sollten mit Vorsicht interpretiert werden.
Despite the superior efficacy of high-dose influenza vaccines, over one-third of older adults fail to respond. Yet, the mechanisms underlying this impaired vaccine responsiveness remain poorly understood. Here, we performed longitudinal profiling of older adults (n=60) receiving high-dose influenza vaccination to identify immune programs associated with vaccine responsiveness. Strong responders exhibited a primed baseline immune state characterized by elevated plasma cytokines and chemokines, followed by enhanced IFN-{gamma} responses and coordinated transcriptional and epigenetic activation of cDC2 cells at day 1. By day 7, CD4+ T-cell trajectories diverged: strong responders preferentially expanded influenza-specific activated cTfh1 (CXCR5+ CXCR3+ ICOS+ CD38+) and influenza-specific Th10 (CXCR5- CXCR3+ PD1+ IL10+) cells, whereas weak responders expanded regulatory cTfr (CXCR5+ FOXP3+) cells. Th10 expansion correlated with plasmablast and antibody responses and was independently validated in a larger influenza vaccination cohort, including younger adults. Functionally, Th10 cells promoted memory B-cell differentiation into plasmablasts and production of influenza-specific IgGs. TCR analyses revealed minimal clonal overlap between Th10 and cTfh1 cells. Together, these findings identify divergent helper and regulatory CD4+ T cell programs associated with vaccine responsiveness and establish Th10 cells as a previously unrecognized component of vaccine-induced humoral immunity.