Construction of the chimeric live attenuated Zika vaccine candidate based on Japanese encephalitis virus
10.3760/cma.j.cn112866-20221214-00255
- VernacularTitle:乙脑病毒为骨架的寨卡病毒减毒活疫苗的构建
- Author:
Liping TANG
1
;
Yang REN
;
Lan CHEN
;
Yueke LI
;
Yalan FENG
;
Rong HUANG
;
Lei YUAN
;
Rong CHEN
;
Jian YANG
Author Information
1. 川北医学院基础医学与法医学院,南充 637000
- Keywords:
Japanese encephalitis virus;
Zika virus;
Chimeric virus;
Vaccine
- From:
Chinese Journal of Experimental and Clinical Virology
2023;37(4):435-442
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To construct the chimeric virus ChimZIKV of Japanese encephalitis virus and Zika virus and evaluate whether the chimeric virus can be developed into a candidate vaccine strain against Zika virus.Methods:The infectious clone of chimeric virus ChimZIKV was constructed by replacement the prM/E of Japanese encephalitis virus vaccine strain with that of Zika virus. RNA of chimeric virus ChimZIKV had been transcribed in vitro and was electro-transfected into BHK-21 cells to rescue chimeric virus. Afterward, the chimeric virus was identified by plaque assay, immunofluorescence and gene sequencing. The growth was shown by the growth curve. The neurobirulence, viremia, neutralizing antibody production and immune protective effect of chimeric virus were tested by animal experiments.Results:The result of restriction enzyme digestion showed that the infectious clone of chimeric virus was successfully constructed, and the immunofluorescence assay and sequencing showed that chimeric virus ChimZIKV was successfully rescued. The cell proliferation activity test showed that the cell proliferation activity of the chimeric virus infected group was higher than that of the infected group. The result of animal experiments showed that chimeric virus showed very low neurovirulence to mice and suckling mice, and the result of viremia showed that chimeric virus had no obvious viremia in mice. Plaque reduction neutralization test (PRNT) showed 100% positive conversion of neutralizing antibody in sera of immunized mice, and the highest neutralizing antibody titer (GMT=85) was seen in the third week. The immune protection experiment showed that the protection rate against JE/ZIKV(MR766) was 30%.Conclusions:This study showed that the chimeric virus ChimZIKV is immunogenic and with low neurovirulence, and it may be further developed as a candidate vaccine strain against Zika virus.