Abstract
The attenuated Japanese encephalitis virus (JEV) live vaccine SA14-14-2 prepared from wild-type (WT) strain SA14 was licensed to prevent Japanese encephalitis (JE) in 1989 in China. Many studies showed that the premembrane (prM) and envelope (E) protein were the crucial determinant of virulence and immunogenicity of JEV. So we are interested in whether the substitution of prM/E of JEV WT SA14 with those of vaccine strain SA14-14-2 could decrease neurovirulence and prevent the challenge of JEV WT SA14. Molecular clone technique was used to replace the prM/E gene of JEV WT strain SA14 with those of vaccine strain SA14-14-2 to construct the infectious clone of chimeric virus (designated JEV SA14/SA14-14-2), the chimeric virus recovered from BHK21 cells upon electrotransfection of RNA into BHK21 cells. The results showed that the recovered chimeric virus was highly attenuated in mice, and a single immunization elicited strong protective immunity in a dose-dependent manner. This study increases our understanding of the molecular mechanisms of neurovirulence attenuation and immunogenicity of JEV.
Highlights
Japanese encephalitis virus (JEV), a mosquito-borne virus, belongs to the Flavivirus genus of the Flaviviridae family, which includes other important virus, such as yellow fever virus (YFV), dengue virus (DENV), and West Nile virus (WNV) [1]
In 1989, a novel live-attenuated JEV vaccine SA1414-2 produced in primary hamster kidney (PHK) cells was licensed in China. is live-attenuated vaccine gradually replaced the inactivated vaccines used previously in China due to its excellent level of safety and efficacy [12]. e JEV SA14-14-2 vaccine has more recently become available in several countries, such as Cambodia, India, South Korea, Laos, Myanmar, Nepal, and ailand, and it has been administered to millions of children with no reported serious adverse events [13,14,15]
Sequence analysis showed there was no any mutant produced in the sequence of chimeric virus compared with SA14-14-2 even in the passage 6th virus. e growth curve of JEV SA14/SA14-14-2 and parental strains JEV SA14 and SA14-14-2 were examined in BHK21 cells
Summary
Japanese encephalitis virus (JEV), a mosquito-borne virus, belongs to the Flavivirus genus of the Flaviviridae family, which includes other important virus, such as yellow fever virus (YFV), dengue virus (DENV), and West Nile virus (WNV) [1]. JEV causes viral encephalitis by attacking nerve cells in the central neurons, astrocytes, and microglial cells [3]. JEV must gain entry to the central nervous system, a process known as neuroinvasiveness of virus, and must replicate and damage the nerve cells, a phenomenon known as neurovirulence [4]. JE is really a vaccine-preventable disease, and inactivated vaccines have been available for ∼50 years [7,8,9]. Due to their relatively high cost in order to achieve adequate immunity, the use of inactivated vaccines is limited in developing countries [10, 11]. In 1989, a novel live-attenuated JEV vaccine SA1414-2 produced in primary hamster kidney (PHK) cells was licensed in China.
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