Liver and Bile
Lancet. 2024;403(10429):813–23
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.