title: Safety and immunogenicity of a freeze-dried, Vero cell culture-derived, inactivated Japanese encephalitis vaccine (KD-287, ENCEVAC®) versus a mouse brain-derived inactivated Japanese encephalitis vaccine in children: a phase III, multicenter, double-blinded, randomized trial.
abstract: BACKGROUND
  Although mouse brain-derived, inactivated Japanese encephalitis vaccines (JE-MBs) have been successfully used for a long time, potential rare neurological complications have prompted the development of a Vero cell culture-derived inactivated vaccine (JE-VC). In a phase III clinical study, we aimed to compare the safety and immunogenicity of a JE-VC, KD-287 with a JE-MB, JEV-GCC, in children.
  
  
  METHODS
  In this multicenter, double-blinded, randomized controlled trial, the study population consisted of 205 healthy Korean children aged 12-23 months. Each subject was subcutaneously vaccinated with either KD-287 or JEV-GCC twice at an interval of 2 weeks and then vaccinated once 12 months after the second vaccination. Neutralizing antibodies were measured by the plaque reduction neutralization test using the homologous and heterologous, as a post hoc analysis, challenge virus strains.
  
  
  RESULTS
  The three-dose regimen of KD-287 showed a comparable safety profile with JEV-GCC except higher incidence of fever after the first dose (30.4% and 14.7%, respectively). Most of the fever was mild degree (61.3% and 66.7%, respectively). KD-287 fulfilled the non-inferiority criteria for seroconversion rate (SCR) and geometric mean titer (GMT) of the neutralizing antibody, which were the primary endpoints, at 4 weeks after the third vaccination (95% CI: -1.00, 3.10 for the SCR difference and 10.8, 17.6 for the GMT ratio). The SCRs of KD-287 were all 100% and the GMTs were higher in the KD-287 group than in the JEV-GCC group after the second vaccination and before and after the third vaccination (GMT ratio: 5.59, 20.13, and 13.79, respectively, p < 0.001 in all). GMTs were higher in the KD-287 group in the heterologous analysis also (GMT ratio: 4.05, 5.15, and 4.19, respectively, p < 0.001 in all).
  
  
  CONCLUSIONS
  This study suggests that the KD-287, a JE-VC is as safe as and may be more effective than the licensed MB-derived vaccine. KD-287 could thus be useful as a second-generation vaccine and substitute for the current JE-MB vaccine in Korean children.
  
  
  BACKGROUND
  ClinicalTrials.gov: NCT01150942.
authors.forename: Ki Wook
authors.initials: KW
authors.lastname: Yun
authors.forename: Hoan Jong
authors.initials: HJ
authors.lastname: Lee
authors.forename: Jin Han
authors.initials: JH
authors.lastname: Kang
authors.forename: Byung Wook
authors.initials: BW
authors.lastname: Eun
authors.forename: Yae-Jean
authors.initials: YJ
authors.lastname: Kim
authors.forename: Kyung-Hyo
authors.initials: KH
authors.lastname: Kim
authors.forename: Nam Hee
authors.initials: NH
authors.lastname: Kim
authors.forename: Young Jin
authors.initials: YJ
authors.lastname: Hong
authors.forename: Dong Ho
authors.initials: DH
authors.lastname: Kim
authors.forename: Hwang Min
authors.initials: HM
authors.lastname: Kim
authors.forename: Sung-Ho
authors.initials: SH
authors.lastname: Cha
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000276:immunology; D000914:Antibodies, Viral / Q000276:immunology; D001921:Brain / Q000821:virology*; D002522:Chlorocebus aethiops; D004311:Double-Blind Method; D004672:Encephalitis, Japanese / Q000276:immunology / Q000821:virology; D005260:Female; D006801:Humans; D007117:Immunization, Secondary; D007223:Infant; D022321:Japanese Encephalitis Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology*; D007723:Korea; D008297:Male; D051379:Mice; D009500:Neutralization Tests; D014611:Vaccination; D015164:Vaccines, Inactivated / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology*; D014709:Vero Cells / Q000821:virology*
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D022321:Japanese Encephalitis Vaccines; D015164:Vaccines, Inactivated