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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 Infect Dis. 2015 Jan 08; 15:7.BI

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.

TRIAL REGISTRATION

ClinicalTrials.gov: NCT01150942.

Authors

No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Clinical Trial, Phase III
Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

25567119

Citation

Yun, Ki Wook, et al. "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, vol. 15, 2015, p. 7.
Yun KW, Lee HJ, Kang JH, et al. 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 Infect Dis. 2015;15:7.
Yun, K. W., Lee, H. J., Kang, J. H., Eun, B. W., Kim, Y. J., Kim, K. H., Kim, N. H., Hong, Y. J., Kim, D. H., Kim, H. M., & Cha, S. H. (2015). 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, 15, 7. https://doi.org/10.1186/s12879-014-0744-4
Yun KW, et al. 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 Infect Dis. 2015 Jan 8;15:7. PubMed PMID: 25567119.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 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. AU - Yun,Ki Wook, AU - Lee,Hoan Jong, AU - Kang,Jin Han, AU - Eun,Byung Wook, AU - Kim,Yae-Jean, AU - Kim,Kyung-Hyo, AU - Kim,Nam Hee, AU - Hong,Young Jin, AU - Kim,Dong Ho, AU - Kim,Hwang Min, AU - Cha,Sung-Ho, Y1 - 2015/01/08/ PY - 2014/02/27/received PY - 2014/12/24/accepted PY - 2015/1/9/entrez PY - 2015/1/9/pubmed PY - 2015/5/23/medline SP - 7 EP - 7 JF - BMC infectious diseases JO - BMC Infect. Dis. VL - 15 N2 - 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. SN - 1471-2334 UR - https://www.unboundmedicine.com/medline/citation/25567119/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_ L2 - https://bmcinfectdis.biomedcentral.com/articles/10.1186/s12879-014-0744-4 DB - PRIME DP - Unbound Medicine ER -