Long-term efficacy of a hepatitis E vaccine.
BACKGROUND
Hepatitis E virus (HEV) is a leading cause of acute hepatitis. The long-term efficacy of a hepatitis E vaccine needs to be determined.


METHODS
In an initial efficacy study, we randomly assigned healthy adults 16 to 65 years of age to receive three doses of either a hepatitis E vaccine (vaccine group; 56,302 participants) or a hepatitis B vaccine (control group; 56,302 participants). The vaccines were administered at 0, 1, and 6 months, and the participants were followed for 19 months. In this extended follow-up study, the treatment assignments of all participants remained double-blinded, and follow-up assessments of efficacy, immunogenicity, and safety were continued for up to 4.5 years.


RESULTS
During the 4.5-year study period, 60 cases of hepatitis E were identified; 7 cases were confirmed in the vaccine group (0.3 cases per 10,000 person-years), and 53 cases in the control group (2.1 cases per 10,000 person-years), representing a vaccine efficacy of 86.8% (95% confidence interval, 71 to 94) in the modified intention-to-treat analysis, rather than (95% confidence interval, 71 to 84) [corrected]. Of the participants who were assessed for immunogenicity and were seronegative at baseline, 87% of those who received three doses of the hepatitis E vaccine maintained antibodies against HEV for at least 4.5 years; HEV antibody titers developed in 9% in the control group. The rate of adverse events was similar in the two groups.


CONCLUSIONS
Immunization with this hepatitis E vaccine induced antibodies against HEV and provided protection against hepatitis E for up to 4.5 years. (Funded by the Chinese Ministry of Science and Technology and others; ClinicalTrials.gov number, NCT01014845.).
From the State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, Collaborative Innovation Center of Biologic Products, School of Public Health, Xiamen University (J.Z., S.-J.H., T.W., J.W.-K.S., M.-H.N., N.-S.X.), and Xiamen Innovax Biotech Company (Q.Y., M.G., X.-H.L., H.-R.P., Y.-M.L.), Xiamen, Jiangsu Provincial Center for Disease Control and Prevention, Nanjing (X.-F.Z., Y.-M.H., H.W., J.-X.L., F.-C.Z.), Dongtai Center for Disease Control and Prevention, Dongtai (Z.-Z.W., H.-M.J., Y.-J.W., C.-L.Y.), and Yancheng Center for Disease Control and Prevention, Yancheng (Q.T., R.-J.J.) - all in China.
Jun
J
Zhang
Xue-Feng
XF
Zhang
Shou-Jie
SJ
Huang
Ting
T
Wu
Yue-Mei
YM
Hu
Zhong-Ze
ZZ
Wang
Hua
H
Wang
Han-Min
HM
Jiang
Yi-Jun
YJ
Wang
Qiang
Q
Yan
Meng
M
Guo
Xiao-Hui
XH
Liu
Jing-Xin
JX
Li
Chang-Lin
CL
Yang
Quan
Q
Tang
Ren-Jie
RJ
Jiang
Hui-Rong
HR
Pan
Yi-Min
YM
Li
J Wai-Kuo
JW
Shih
Mun-Hon
MH
Ng
Feng-Cai
FC
Zhu
Ning-Shao
NS
Xia
D000293:Adolescent; D000328:Adult; D000368:Aged; D004311:Double-Blind Method; D005260:Female; D005838:Genotype; D006508:Hepatitis Antibodies / Q000097:blood; D016751:Hepatitis E / Q000276:immunology / Q000517:prevention & control*; D016752:Hepatitis E virus / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D008297:Male; D008875:Middle Aged; D013997:Time Factors; D014761:Viral Hepatitis Vaccines / Q000009:adverse effects / Q000276:immunology*; D055815:Young Adult
D006508:Hepatitis Antibodies; D007074:Immunoglobulin G; D014761:Viral Hepatitis Vaccines