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

doi:10.1038/s41541-020-00220-4

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

NPJ Vaccines. 2020 Aug 5;5(1):73. doi: 10.1038/s41541-020-00220-4. eCollection 2020.

Authors

Na Li^{1

2}, Zhe-Rui Zhang^{1

2}, Ya-Nan Zhang^{1

2}, Jing Liu^{1

2}, Cheng-Lin Deng¹, Pei-Yong Shi³, Zhi-Ming Yuan¹, Han-Qing Ye¹, Bo Zhang^{1

4}

Affiliations

¹ Key Laboratory of Special Pathogens and Biosafety, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, China.
² University of Chinese Academy of Sciences, 100049 Beijing, China.
³ Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, TX 77555 USA.
⁴ Drug Discovery Center for Infectious Disease, Nankai University, 300350 Tianjin, China.

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 (BHK_NS1) 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.

Keywords: Live attenuated vaccines; Vaccines.