Long-term protection from naturally acquired immunity against hepatitis E virus reinfection
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.
Authors
- Ting Wu (ORCID: https://orcid.org/0000-0002-1806-3056)
- Xingcheng Huang (ORCID: https://orcid.org/0000-0003-0578-0088)
- Chunlan Zhuang (ORCID: https://orcid.org/0000-0002-8253-2515)
- Xiaowen Hu (ORCID: https://orcid.org/0000-0002-3727-6049)
- Wenhua Zhu (ORCID: https://orcid.org/0000-0001-8011-0274)
- Changlin Yang (ORCID: https://orcid.org/0000-0003-1352-7429)
- Xia Zang
- Kongxin Zhu
- Zizheng Zheng (ORCID: https://orcid.org/0000-0003-0099-4212)
- Ningshao Xia (ORCID: https://orcid.org/0000-0003-0179-5266)
- Xiaohui Liu (ORCID: https://orcid.org/0000-0003-1828-0162)
- Jun Zhang (ORCID: https://orcid.org/0000-0002-6601-9180)
- Yijun Wang (ORCID: https://orcid.org/0000-0001-5815-7172)
- Yingying Su (ORCID: https://orcid.org/0000-0003-3883-357X)
- Donglin Liu (ORCID: https://orcid.org/0009-0001-8413-0202)
- Shoujie Huang (ORCID: https://orcid.org/0000-0001-5012-2274)
- Zhaofeng Bi
- Qi Chen (ORCID: https://orcid.org/0009-0006-5926-7457)
- Han-Min Jiang
Institutions
- Xiamen University (CN)
- Chinese Academy of Medical Sciences & Peking Union Medical College (CN)
Publication Details
- Journal
- Nature Communications
- Published
- 2025-12-17
- DOI
- https://doi.org/10.1038/s41467-025-66188-8
- Primary Topic
- Hepatitis Viruses Studies and Epidemiology
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- National Natural Science Foundation of China
- China Postdoctoral Science Foundation
- Natural Science Foundation of Fujian Province
- Fundamental Research Funds for the Central Universities