Long-term protection from naturally acquired immunity against hepatitis E virus reinfection.
- 2025-12-17
- Nature communications 16(1)
- Xiaohui Liu
- Xia Zang
- Kongxin Zhu
- Xingcheng Huang
- Xiaowen Hu
- Zhaofeng Bi
- Qi Chen
- Hanmin Jiang
- Yijun Wang
- Changlin Yang
- Donglin Liu
- Wenhua Zhu
- Zizheng Zheng
- Yingying Su
- Ting Wu
- Shoujie Huang
- Chunlan Zhuang
- Jun Zhang
- Ningshao Xia
- PubMed: 41407683
- DOI: 10.1038/s41467-025-66188-8
Study Design
- Type
- Randomized Controlled Trial (RCT)
- Sample size
- n = 3,838
- Population
- 7032 adult placebo recipients (aged 16 to 65 years) from a phase 3 HEV vaccine trial in China
- Methods
- 103-month longitudinal analysis of placebo recipients from a phase 3 HEV vaccine trial
- Duration
- 103 months
- Funding
- Unclear
- Large Human Trial
- Rigorous Journal
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.