Long-term protection from naturally acquired immunity against hepatitis E virus reinfection

作者：Xiaohui Liu, Xia Zang, Kongxin Zhu, Xingcheng Huang, Xiaowen Hu, Zhaofeng Bi, Qi Chen, Han-Min Jiang, Yijun Wang, Changlin Yang, Donglin Liu, Wenhua Zhu, Zizheng Zheng, Yingying Su, Ting Wu, Shoujie Huang, Chunlan Zhuang, Jun Zhang, Ningshao Xia · 发表于：Nature Communications · 年份：2025 · DOI：10.1038/s41467-025-66188-8 · 被引用次数：2 · 研究领域：Hepatitis Viruses Studies and Epidemiology、Viral Infections and Immunology Research、Travel-related health issues

The durability and protective effect of naturally acquired antibodies against hepatitis E virus (HEV) reinfection and clinical progression remain unclear in humans. In a 103-month longitudinal analysis of 7032 adult placebo recipients (aged 16 to 65 years) from a phase 3 HEV vaccine trial in China, we demonstrated that baseline anti-HEV IgG seropositivity (n = 3194) conferred over 50% higher protection against reinfection compared with seronegative individuals (n = 3838), with this protective effect remaining consistent over 8.5 years. A non-linear dose-response relationship was observed, whereby baseline anti-HEV IgG concentrations ≥0.25 WHO units/mL were associated with at least a 50% reduction in infection risk, with higher baseline antibody levels correlated with a lower risk of infection. Natural immunity provided approximately 70% protection against clinically apparent hepatitis E in the cohort, with 10 symptomatic cases identified over a decade of active surveillance. Six were hospitalized, all of whom were baseline seronegative. These findings establish that natural HEV immunity provides durable, though incomplete, protection. Hepatitis E virus is a leading cause of acute viral hepatitis and antibodies can persist for years post-infection. Here, the authors quantify the protective effects of naturally acquired immunity against subclinical and clinical hepatitis E infection using data from a placebo arm of a vaccine trial in China.