Efficacy and safety of a recombinant hepatitis E vaccine in healthy adults: a
large-scale, randomised, double-blind placebo-controlled, phase 3 trial.
Author(s): Zhu FC, Zhang J, Zhang XF, Zhou C, Wang ZZ, Huang SJ, Wang H, Yang CL, Jiang HM,
Cai JP, Wang YJ, Ai X, Hu YM, Tang Q, Yao X, Yan Q, Xian YL, Wu T, Li YM, Miao J,
Ng MH, Shih JW, Xia NS.
Affiliation(s): Jiangsu Provincial Centre for Disease Control and Prevention, Nanjing, Jiangsu
Province, China.
Publication date & source: 2010, Lancet. , 376(9744):895-902
BACKGROUND: Seroprevalence data suggest that a third of the world's population
has been infected with the hepatitis E virus. Our aim was to assess efficacy and
safety of a recombinant hepatitis E vaccine, HEV 239 (Hecolin; Xiamen Innovax
Biotech, Xiamen, China) in a randomised, double-blind, placebo-controlled, phase
3 trial.
METHODS: Healthy adults aged 16-65 years in, Jiangsu Province, China were
randomly assigned in a 1:1 ratio to receive three doses of HEV 239 (30 microg of
purified recombinant hepatitis E antigen adsorbed to 0.8 mg aluminium hydroxide
suspended in 0.5 mL buffered saline) or placebo (hepatitis B vaccine) given
intramuscularly at 0, 1, and 6 months. Randomisation was done by
computer-generated permuted blocks and stratified by age and sex. Participants
were followed up for 19 months. The primary endpoint was prevention of hepatitis
E during 12 months from the 31st day after the third dose. Analysis was based on
participants who received all three doses per protocol. Study participants, care
givers, and investigators were all masked to group and vaccine assignments. This
trial is registered with ClinicalTrials.gov, number NCT01014845.
FINDINGS: 11,165 of the trial participants were tested for hepatitis E virus IgG,
of which 5285 (47%) were seropositive for hepatitis E virus. Participants were
randomly assigned to vaccine (n=56,302) or placebo (n=56,302). 48,693 (86%)
participants in the vaccine group and 48,663 participants (86%) in the placebo
group received three vaccine doses and were included in the primary efficacy
analysis. During the 12 months after 30 days from receipt of the third dose 15
per-protocol participants in the placebo group developed hepatitis E compared
with none in the vaccine group. Vaccine efficacy after three doses was 100.0%
(95% CI 72.1-100.0). Adverse effects attributable to the vaccine were few and
mild. No vaccination-related serious adverse event was noted.
INTERPRETATION: HEV 239 is well tolerated and effective in the prevention of
hepatitis E in the general population in China, including both men and women age
16-65 years.
FUNDING: Chinese National High-tech R&D Programme (863 programme), Chinese
National Key Technologies R&D Programme, Chinese National Science Fund for
Distinguished Young Scholars, Fujian Provincial Department of Sciences and
Technology, Xiamen Science and Technology Bureau, and Fujian Provincial Science
Fund for Distinguished Young Scholars.
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