全氟化合物（PFASs）是一类在环境和人体中广泛存在的新型有机污染物，已有研究证实它具有免疫毒性，但毒性机制不明确。申请人课题组在前期建立的出生队列研究中发现脐带血典型PFASs的暴露与新生儿某些疫苗抗体水平呈负相关，异构体的效应比直链更为显著。因此，本项目在已建立的出生队列基础上，以人群暴露-动物模型-风险评估为主线，探讨生命早期PFASs暴露对儿童疫苗免疫应答的影响及机制。开展分子流行病学研究检测儿童外周血淋巴细胞免疫平衡，表征PFASs内暴露谱，结合疫苗免疫动物模型，利用转录组测序和基因组DNA甲基化谱筛查特异、可调控的表观遗传生物学标志。应用贝叶斯网络模型建立暴露与生物标志物的相关关系，通过剂量—反应关系分析筛查疫苗免疫应答的关键靶点，为探讨PFASs的免疫调控机制，开展儿童PFASs暴露的健康风险评估提供科学依据。

Perfluoroalkyl substances are one of the persistent organic pollutants which can be widely detected in the environmental as well as humans. Immunotoxic effects of PFASs exposure have been found. However, the mechanism is still uncovered. Our previous study has preliminarily suggested the adverse association between prenatal exposure of PFASs and some vaccine responses, with more significant correlation in PFASs isomer exposure. Therefore, this project aims to investigate the mechanism involves in the vaccine antibody responses to prenatal exposure of PFASs in children from the established birth cohort study. Molecular epidemiological approaches are applied to investigate the immune balance in peripheral blood mononuclear cell and exposure fingerprint of PFASs in children. In combine with animal immune response model, DNA microarray and genomic DNA methylation profiles are employed to explore the feasibility of the variation of epigenetic patterns as novel biomarkers to predict the PFASs exposure and immune response. Bayesian network model is applied to analyze the correlation between prenatal PFASs exposure and the biological effects. Our goals devote to screening the key targets in the vaccine immune response to PFASs by analysis of dose-response relationship, investigating the mechanism involved in the immune response, and laying the foundation for health risk assessment in children to the PFASs exposure.