Liver and Bile

Lancet. 2024;403(10429):813–23

Huang S, Zhang X, Su Y, Zhuang C, Tang Z, Huang X, Chen Q, Zhu K, Hu X, Ying D, Liu X, Jiang H, Zang X, Wang Z, Yang C, Liu D, Wang Y, Tang Q, Shen W, Cao H, Pan H, Ge S, Huang Y, Wu T, Zheng Z, Zhu F, Zhang J, Xia N

Long-term efficacy of a recombinant hepatitis E vaccine in adults: 10-year results from a randomized, double-blind, placebo-controlled, phase 3 trial

Background: Hepatitis E virus is a frequently overlooked causative agent of acute hepatitis. Evaluating the long-term durability of hepatitis E vaccine efficacy holds crucial importance.
Methods: This study was an extension to a randomized, double-blind, placebo-controlled, phase-3 clinical trial of the hepatitis E vaccine conducted in Dongtai County, Jiangsu, China. Participants were recruited from 11 townships in Dongtai County. In the initial trial, a total of 112,604 healthy adults aged 16–65 years were enrolled, stratified according to age and sex, and randomly assigned in a 1:1 ratio to receive 3 doses of hepatitis E vaccine or placebo intramuscularly at month 0, month 1, and month 6. A sensitive hepatitis E surveillance system including 205 clinical sentinels, covering the entire study region, was established and maintained for 10 years after vaccination. The primary outcome was the per-protocol efficacy of hepatitis E vaccine to prevent confirmed hepatitis E occurring at least 30 days after administration of the third dose. Throughout the study, the participants, site investigators, and laboratory staff remained blinded to the treatment assignments.
Findings: During the 10-year study period from August 22, 2007, to October 31, 2017, 90 people with hepatitis E were identified; 13 in the vaccine group (0.2 per 10,000 person-years) and 77 in the placebo group (1.4 per 10,000 person-years), corresponding to a vaccine efficacy of 83.1% (95% confidence interval [CI]: 69.4–91.4) in the modified intention-to-treat analysis and 86.6% (95% CI: 73.0–94.1) in the per-protocol analysis. In the subsets of participants assessed for immunogenicity persistence, of those who were seronegative at baseline and received 3 doses of hepatitis E vaccine, 254 of 291 vaccinees (87.3%) in Qindong at the 8.5-year mark and 1270 of 1740 vaccinees (73.0%) in Anfeng at the 7.5-year mark maintained detectable concentrations of antibodies.

Interpretation: Immunization with this hepatitis E vaccine offers durable protection against hepatitis E for up to 10 years, with vaccine-induced antibodies against hepatitis E virus persisting for at least 8.5 years.

DOI: 10.1016/s0140-6736(23)02234-1