A replication-defective Japanese encephalitis virus (JEV) vaccine candidate with NS1 deletion confers dual protection against JEV and West Nile virus in mice

Na Li, Zhe Rui Zhang, Ya Nan Zhang, Jing Liu, Cheng Lin Deng, Pei Yong Shi, Zhi Ming Yuan, Han Qing Ye, Bo Zhang

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Article number73
Journalnpj Vaccines
Volume5
Issue number1
DOIs
StatePublished - Dec 1 2020

ASJC Scopus subject areas

  • Immunology
  • Pharmacology
  • Infectious Diseases
  • Pharmacology (medical)

Fingerprint Dive into the research topics of 'A replication-defective Japanese encephalitis virus (JEV) vaccine candidate with NS1 deletion confers dual protection against JEV and West Nile virus in mice'. Together they form a unique fingerprint.

  • Cite this