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

BMC Infectious Diseases

Sung-Ho Cha^1,10  Hwang Min Kim⁵  Dong Ho Kim⁷  Young Jin Hong⁸  Nam Hee Kim⁶  Kyung-Hyo Kim²  Yae-Jean Kim⁴  Byung Wook Eun³  Jin Han Kang¹  Hoan Jong Lee⁹  Ki Wook Yun^1,11 

[1] Department of Pediatrics, College of Medicine, The Catholic University of Korea, Seoul, Korea;Department of Pediatrics, School of Medicine, Ewha Womans University, Seoul, Korea;Department of Pediatrics, Eulji General Hospital, Eulji University School of Medicine, Seoul, Korea;Departments of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea;Department of Pediatrics, Yonsei University Wonju College of Medicine, Wonju, Korea;Department of Pediatrics, Ilsan Paik Hospital, Inje University College of Medicine, Goyang, Korea;Department of Pediatrics, Korea Cancer Center Hospital, Seoul, Korea;Department of Pediatrics, Inha University College of Medicine, Incheon, Korea;Department of Pediatrics, Seoul National University College of Medicine, Seoul, Korea;Department of Pediatrics, College of Medicine, Kyunghee University, Seoul, Korea;Department of Pediatrics, Chung-Ang University College of Medicine, Seoul, Korea

关键词: Clinical trial;    Vero cells;    Vaccine;    Japanese encephalitis;   

Others  :  1089925
DOI  :  10.1186/s12879-014-0744-4

 received in 2014-02-27, accepted in 2014-12-24,  发布年份 2015

【 摘 要 】

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.

Trial registration

ClinicalTrials.gov: NCT01150942 webcite

【 授权许可】

   
2015 Yun et al.; licensee BioMed Central.

【 图 表 】

Figure 1.

Figure 2.

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