Basal T cell activation predicts yellow fever vaccine response independently of cytomegalovirus infection and sex-related immune variations.

IF 11.7 1区医学 Q1 CELL BIOLOGY

Cell Reports Medicine Pub Date : 2025-02-18 Epub Date: 2025-02-11 DOI:10.1016/j.xcrm.2025.101946

Antonio Santos-Peral, Magdalena Zaucha, Elena Nikolova, Ekin Yaman, Barbara Puzek, Elena Winheim, Sebastian Goresch, Magdalena K Scheck, Lisa Lehmann, Frank Dahlstroem, Hadi Karimzadeh, Julia Thorn-Seshold, Shenzhi Jia, Fabian Luppa, Michael Pritsch, Julia Butt, Camila Metz-Zumaran, Giovanna Barba-Spaeth, Stefan Endres, Sarah Kim-Hellmuth, Tim Waterboer, Anne B Krug, Simon Rothenfusser

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Abstract

The live-attenuated yellow fever 17D (YF17D) vaccine is a model of acute viral infection that induces long-lasting protective immunity. Among immunocompetent adults, responses to YF17D vary significantly. To understand the sources of this variability, we investigate the influence of sex, age, human leukocyte antigen (HLA) type, and 20 prior infections on basal immune parameters and the cellular and antibody response to YF17D in 250 healthy young individuals. Multivariate regression found that sex and cytomegalovirus (CMV) infection significantly contribute to baseline immune variation but do not affect vaccine responses except for reduced YF17D-specific CD8⁺ frequencies in CMV-infected males. However, the abundance at baseline of non-specific cytokine-expressing T helper cells in circulation is associated with stronger vaccine responses, a state that smoking favors. Additionally, an elevated baseline level of interferon-stimulated CXCL10 is linked to poorer vaccination outcomes. Altogether, YF17D reactivity is conditioned by the baseline immune status independent of sex and CMV-related variations.

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基底T细胞激活预测黄热病疫苗反应独立于巨细胞病毒感染和性别相关的免疫变异。

黄热病17D减毒活疫苗是一种急性病毒感染的模型，可诱导持久的保护性免疫。在免疫功能正常的成年人中，对YF17D的反应差异很大。为了了解这种变异的来源，我们调查了250名健康年轻人的性别、年龄、人类白细胞抗原（HLA）类型和20例既往感染对基础免疫参数以及细胞和抗体对YF17D的反应的影响。多因素回归发现，性别和巨细胞病毒（CMV）感染显著影响基线免疫变异，但不影响疫苗应答，除了巨细胞病毒感染的男性中yf17d特异性CD8+频率降低。然而，血液循环中表达非特异性细胞因子的辅助性T细胞的基线丰度与更强的疫苗应答有关，而吸烟有利于这种状态。此外，干扰素刺激的CXCL10基线水平升高与较差的疫苗接种结果有关。总之，YF17D反应性是由独立于性别和cmv相关变异的基线免疫状态决定的。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cell Reports Medicine Biochemistry, Genetics and Molecular Biology-Biochemistry, Genetics and Molecular Biology (all)

CiteScore

15.00

自引率

1.40%

发文量

231

审稿时长

40 days

期刊介绍： Cell Reports Medicine is an esteemed open-access journal by Cell Press that publishes groundbreaking research in translational and clinical biomedical sciences, influencing human health and medicine. Our journal ensures wide visibility and accessibility, reaching scientists and clinicians across various medical disciplines. We publish original research that spans from intriguing human biology concepts to all aspects of clinical work. We encourage submissions that introduce innovative ideas, forging new paths in clinical research and practice. We also welcome studies that provide vital information, enhancing our understanding of current standards of care in diagnosis, treatment, and prognosis. This encompasses translational studies, clinical trials (including long-term follow-ups), genomics, biomarker discovery, and technological advancements that contribute to diagnostics, treatment, and healthcare. Additionally, studies based on vertebrate model organisms are within the scope of the journal, as long as they directly relate to human health and disease.