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A replication-defective Japanese encephalitis virus (JEV) vaccine candidate with NS1 deletion confers dual protection against JEV and West Nile virus in mice
- Source :
- npj Vaccines, Vol 5, Iss 1, Pp 1-10 (2020), NPJ Vaccines
- Publication Year :
- 2020
- Publisher :
- Nature Publishing Group, 2020.
-
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.
- 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
Subjects
Details
- Language :
- English
- ISSN :
- 20590105
- Volume :
- 5
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- npj Vaccines
- Accession number :
- edsair.doi.dedup.....b437355a1c3f38ef6c53912d97f2c24c