title: Safety and efficacy of a recombinant hepatitis E vaccine.
abstract: 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].).
authors.affiliation: Walter Reed-Armed Forces Research Institute of Medical Sciences Research Unit Nepal, Kathmandu, Nepal.
authors.forename: Mrigendra Prasad
authors.initials: MP
authors.lastname: Shrestha
authors.forename: Robert McNair
authors.initials: RM
authors.lastname: Scott
authors.forename: Durga Man
authors.initials: DM
authors.lastname: Joshi
authors.forename: Mammen P
authors.initials: MP
authors.lastname: Mammen
authors.forename: Gyan Bahadur
authors.initials: GB
authors.lastname: Thapa
authors.forename: Narbada
authors.initials: N
authors.lastname: Thapa
authors.forename: Khin Saw Aye
authors.initials: KS
authors.lastname: Myint
authors.forename: Marc
authors.initials: M
authors.lastname: Fourneau
authors.forename: Robert A
authors.initials: RA
authors.lastname: Kuschner
authors.forename: Sanjaya Kumar
authors.initials: SK
authors.lastname: Shrestha
authors.forename: Marie Pierre
authors.initials: MP
authors.lastname: David
authors.forename: Jitvimol
authors.initials: J
authors.lastname: Seriwatana
authors.forename: David W
authors.initials: DW
authors.lastname: Vaughn
authors.forename: Assad
authors.initials: A
authors.lastname: Safary
authors.forename: Timothy P
authors.initials: TP
authors.lastname: Endy
authors.forename: Bruce L
authors.initials: BL
authors.lastname: Innis
mesh_terms: 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
chemical_list: D006508:Hepatitis Antibodies; D014614:Vaccines, Synthetic; D014761:Viral Hepatitis Vaccines