Immunogenicity, Genetic Stability, and Protective Efficacy of a Recombinant, Chimeric Yellow Fever-Japanese Encephalitis Virus (ChimeriVax-JE) as a Live, Attenuated Vaccine Candidate against Japanese Encephalitis

Japanese encephalitis virus (JEV) is the leading cause of viral encephalitis worldwide. Annually it causes between 13,000 and 20,000 deaths mainly in South-East Asia. Vaccination programmes have drastically reduced the number of JEV cases however outbreaks do still occur. Recently G1 has overtaken G3 as the dominant genotype in most endemic countries and as all currently licensed vaccines are based on G3 it is necessary to evaluate the potential of emerging genotypes to break through current control measures. This project seeks to generate a virus-like-particle (VLP) neutralisation assay in order to investigate the potential for emergent or divergent genotypes of JEV to infect vaccinated individuals. Using this assay, we will evaluate the ability of vaccinee sera to neutralise emergent genotypes as well as to introduce a variety of SNPs that have been shown to enhance virulence and investigate whether any combination of these are able to invalidate vaccine protection. There is also concern that recombination between wild-type and live attenuated vaccine strains may occur in the vaccine setting which could result in rescue of the virulent potential of the attenuated virus. Evidence of this is being sought in silico using publicly available data and existing techniques. These data will provide a clearer picture of the nature of JEV in endemic areas and whether the current strategy of vaccination is sufficient to prevent naturally acquired infection in the long term or if other strategies must now be considered.

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

10.21203/rs.2.20138/v1 ◽

2020 ◽

Author(s):

Ran Wang ◽

Xiaozheng Yu ◽

Yan Wang ◽

Xiaoyan Zheng

Keyword(s):

Japanese Encephalitis Virus ◽

Dna Vaccine ◽

Japanese Encephalitis ◽

Protective Efficacy ◽

Neutralizing Antibody ◽

Encephalitis Virus ◽

Inactivated Vaccine ◽

Complete Protection ◽

Igg Antibody ◽

Humoral Immune

Abstract Background The incidence of Japanese encephalitis (JE) has been dramatically reduced in China after the coverage of the vaccine. It is believed that the live-attenuated Japanese encephalitis virus (JEV) vaccine SA14-14-2 has contributed a lot. Another vaccine that seems to have faded out of the public is an inactivated vaccine based on the JEV P3 strain, which is still considered to have certain modifiability, such as being transformed into a DNA vaccine to improve its immunogenicity. Methods In this study, the protective efficacy induced by a Japanese encephalitis DNA vaccine candidate pV-JP3ME encoding pre-membrane (prM) and envelope (E) proteins of P3 strain in BALB/c mice. The prM/E genes of the JEV P3 strain were subcloned into vector pVAX1 (pV) to construct pV-JP3ME. Results The plasmid DNA was immunized BALB/c mice, high titers of IgG antibody and neutralizing antibody (nAb) against JEV were detected. The key cytokines in splenocytes upon stimulation with JEV antigens were secreted. Finally, complete protective efficacy was generated after challenge with the JEV P3 strain in mice. Conclusions The DNA vaccine pV-JP3ME based on JEV P3 strain in this study can induce specific humoral immune and cytokine responses in mice, and provide complete protection for mice against JEV.

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A highly pathogenic porcine reproductive and respiratory syndrome virus candidate vaccine based on Japanese encephalitis virus replicon system

PeerJ ◽

10.7717/peerj.3514 ◽

2017 ◽

Vol 5 ◽

pp. e3514 ◽

Cited By ~ 1

Author(s):

Pingsheng Hu ◽

Xiaoming Chen ◽

Lihong Huang ◽

Shukai Liu ◽

Fuyu Zang ◽

...

Keyword(s):

Japanese Encephalitis Virus ◽

Japanese Encephalitis ◽

Vaccine Candidate ◽

Expression System ◽

Ectopic Expression ◽

Encephalitis Virus ◽

Economic Losses ◽

Respiratory Syndrome Virus ◽

Response Analysis ◽

Effective Prevention

In the swine industry, porcine reproductive and respiratory syndrome (PRRS) is a highly contagious disease which causes heavy economic losses worldwide. Effective prevention and disease control is an important issue. In this study, we described the construction of a Japanese encephalitis virus (JEV) DNA-based replicon with a cytomegalovirus (CMV) promoter based on the genome of Japanese encephalitis live vaccine virus SA14-14-2, which is capable of offering a potentially novel way to develop and produce vaccines against a major pathogen of global health. This JEV DNA-based replicon contains a large deletion in the structural genes (C-prM-E). A PRRSV GP5/M was inserted into the deletion position of JEV DNA-based replicons to develop a chimeric replicon vaccine candidate for PRRSV. The results showed that BALB/c mice models with the replicon vaccines pJEV-REP-G-2A-M-IRES and pJEV-REP-G-2A-M stimulated antibody responses and induced a cellular immune response. Analysis of ELSA data showed that vaccination with the replicon vaccine expressing GP5/M induced a better antibodies response than traditional DNA vaccines. Therefore, the results suggested that this ectopic expression system based on JEV DNA-based replicons may represent a useful molecular platform for various biological applications, and the JEV DNA-based replicons expressing GP5/M can be further developed into a novel, safe vaccine candidate for PRRS.

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