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Complete protection for mice conferred by a DNA vaccine based on the Japanese encephalitis virus P3 strain used to prepare the inactivated vaccine in China.

ABSTRACT: BACKGROUND:The incidence of Japanese encephalitis (JE) has been dramatically reduced in China after sufficient vaccine coverage. The live-attenuated Japanese encephalitis virus (JEV) vaccine SA14-14-2 is believed to have strongly contribute to this decrease. Another vaccine that seems to have decreased in importance is an inactivated vaccine based on the JEV P3 strain, which is considered to be modifiable, such as being transformed into a DNA vaccine to improve its immunogenicity. METHODS:In this study, the protective efficacy induced by the Japanese encephalitis DNA vaccine candidate pV-JP3ME encoding the premembrane (prM) and envelope (E) proteins of the P3 strain was assessed in BALB/c mice. The prM/E genes of the JEV P3 strain were subcloned into the vector pVAX1 (pV) to construct pV-JP3ME. RESULTS:The plasmid DNA was immunized into BALB/c mice, and high titers of IgG antibody and neutralizing antibody (nAb) against JEV were detected. The key cytokines in splenocytes were secreted upon stimulation with JEV antigens. Finally, complete protective efficacy was generated after challenge with the JEV P3 strain in the mice. CONCLUSIONS:The DNA vaccine pV-JP3ME based on the JEV P3 strain in this study can induce specific humoral immune and cytokine responses and provide complete protection against JEV in mice.

SUBMITTER: Zheng X

PROVIDER: S-EPMC7444069 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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Complete protection for mice conferred by a DNA vaccine based on the Japanese encephalitis virus P3 strain used to prepare the inactivated vaccine in China.

Zheng Xiaoyan X Yu Xiaozheng X Wang Yan Y Turtle Lance L Cui Min M Wang Ran R Yin Chenghong C

Virology journal 20200824 1

<h4>Background</h4>The incidence of Japanese encephalitis (JE) has been dramatically reduced in China after sufficient vaccine coverage. The live-attenuated Japanese encephalitis virus (JEV) vaccine SA14-14-2 is believed to have strongly contribute to this decrease. Another vaccine that seems to have decreased in importance is an inactivated vaccine based on the JEV P3 strain, which is considered to be modifiable, such as being transformed into a DNA vaccine to improve its immunogenicity.<h4>Met ...[more]

PMID: 32831096

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Project description: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.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.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).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.ClinicalTrials.gov: NCT01150942.

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Complete protection for mice conferred by a DNA vaccine based on the Japanese encephalitis virus P3 strain used to prepare the inactivated vaccine in China.

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Complete protection for mice conferred by a DNA vaccine based on the Japanese encephalitis virus P3 strain used to prepare the inactivated vaccine in China.

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