Safety and efficacy of a recombinant hepatitis E vaccine.
BACKGROUND
Hepatitis E virus (HEV) is an important cause of viral hepatitis. We evaluated the safety and efficacy of an HEV recombinant protein (rHEV) vaccine in a phase 2, randomized, double-blind, placebo-controlled trial.


METHODS
In Nepal, we studied 2000 healthy adults susceptible to HEV infection who were randomly assigned to receive three doses of either the rHEV vaccine or placebo at months 0, 1, and 6. Active (including hospital) surveillance was used to identify acute hepatitis and adverse events. The primary end point was the development of hepatitis E after three vaccine doses.


RESULTS
A total of 1794 subjects (898 in the vaccine group and 896 in the placebo group) received three vaccine doses; the total vaccinated cohort was followed for a median of 804 days. After three vaccine doses, hepatitis E developed in 69 subjects, of whom 66 were in the placebo group. The vaccine efficacy was 95.5% (95% confidence interval [CI], 85.6 to 98.6). In an intention-to-treat analysis that included all 87 subjects in whom hepatitis E developed after the first vaccine dose, 9 subjects were in the vaccine group, with a vaccine efficacy of 88.5% (95% CI, 77.1 to 94.2). Among subjects in a subgroup randomly selected for analysis of injection-site findings and general symptoms (reactogenicity subgroup) during the 8-day period after the administration of any dose, the proportion of subjects with adverse events was similar in the two study groups, except that injection-site pain was increased in the vaccine group (P=0.03).


CONCLUSIONS
In a high-risk population, the rHEV vaccine was effective in the prevention of hepatitis E. (ClinicalTrials.gov number, NCT00287469 [ClinicalTrials.gov].).
Shrestha
Mrigendra Prasad
MP
Walter Reed-Armed Forces Research Institute of Medical Sciences Research Unit Nepal, Kathmandu, Nepal.
Scott
Robert McNair
RM
Joshi
Durga Man
DM
Mammen
Mammen P
MP
Thapa
Gyan Bahadur
GB
Thapa
Narbada
N
Myint
Khin Saw Aye
KS
Fourneau
Marc
M
Kuschner
Robert A
RA
Shrestha
Sanjaya Kumar
SK
David
Marie Pierre
MP
Seriwatana
Jitvimol
J
Vaughn
David W
DW
Safary
Assad
A
Endy
Timothy P
TP
Innis
Bruce L
BL
D000293:Adolescent; D000328:Adult; D005260:Female; D006508:Hepatitis Antibodies / Q000097:blood; D016751:Hepatitis E / Q000453:epidemiology / Q000517:prevention & control*; D016752:Hepatitis E virus / Q000276:immunology; D006801:Humans; D015994:Incidence; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology; D014761:Viral Hepatitis Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology
D006508:Hepatitis Antibodies; D014614:Vaccines, Synthetic; D014761:Viral Hepatitis Vaccines