1. A replication-defective Japanese encephalitis virus (JEV) vaccine candidate with NS1 deletion confers dual protection against JEV and West Nile virus in mice
- Author
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Zhiming Yuan, Ya-Nan Zhang, Na Li, Pei Yong Shi, Zhe Rui Zhang, Cheng Lin Deng, Bo Zhang, Jing Liu, and Han-Qing Ye
- Subjects
0301 basic medicine ,lcsh:Immunologic diseases. Allergy ,Live attenuated vaccines ,viruses ,030231 tropical medicine ,Immunology ,Heterologous ,Context (language use) ,Viremia ,Biology ,lcsh:RC254-282 ,Virus ,Article ,03 medical and health sciences ,0302 clinical medicine ,Immune system ,medicine ,Pharmacology (medical) ,Pharmacology ,Vaccines ,virus diseases ,Japanese encephalitis ,medicine.disease ,biology.organism_classification ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Virology ,Flavivirus ,030104 developmental biology ,Infectious Diseases ,Immunization ,lcsh:RC581-607 - Abstract
In our previous study, we have demonstrated in the context of WNV-ΔNS1 vaccine (a replication-defective West Nile virus (WNV) lacking NS1) that the NS1 trans-complementation system may offer a promising platform for the development of safe and efficient flavivirus vaccines only requiring one dose. Here, we produced high titer (107 IU/ml) replication-defective Japanese encephalitis virus (JEV) with NS1 deletion (JEV-ΔNS1) in the BHK-21 cell line stably expressing NS1 (BHKNS1) using the same strategy. JEV-ΔNS1 appeared safe with a remarkable genetic stability and high degrees of attenuation of in vivo neuroinvasiveness and neurovirulence. Meanwhile, it was demonstrated to be highly immunogenic in mice after a single dose, providing similar degrees of protection to SA14-14-2 vaccine (a most widely used live attenuated JEV vaccine), with healthy condition, undetectable viremia and gradually rising body weight. Importantly, we also found JEV-ΔNS1 induced robust cross-protective immune responses against the challenge of heterologous West Nile virus (WNV), another important member in the same JEV serocomplex, accounting for up to 80% survival rate following a single dose of immunization relative to mock-vaccinated mice. These results not only support the identification of the NS1-deleted flavivirus vaccines with a satisfied balance between safety and efficacy, but also demonstrate the potential of the JEV-ΔNS1 as an alternative vaccine candidate against both JEV and WNV challenge.
- Published
- 2020