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Novel Japanese encephalitis virus NS1-based vaccine: Truncated NS1 fused with E. coli heat labile enterotoxin B subunit

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Background Current vaccines against Japanese encephalitis virus (JEV) of flaviviruses have some disadvantages, such as the risk of virulent reversion. Non-structural protein NS1 is conserved among flaviviruses and confers immune… Click to show full abstract

Background Current vaccines against Japanese encephalitis virus (JEV) of flaviviruses have some disadvantages, such as the risk of virulent reversion. Non-structural protein NS1 is conserved among flaviviruses and confers immune protection without the risk of antibody-dependent enhancement (ADE). Therefore, NS1 has become a promising vaccine candidate against flaviviruses. Methods A NS1-based vaccine (LTB-NS1∆63) with a truncated NS1 protein (NS1∆63) fused to E. coli heat-labile enterotoxin B subunit (LTB) was expressed in E.coli and explored for its ability to induce immune responses. Safety of LTB-NS1∆63 was assessed by determining its toxicity in vitro and in vivo. Protective capability of LTB-NS1∆63 and its-induced antisera was evaluated in the mice challenged with JEV by analyzing mortality and morbidity. Findings LTB-NS1∆63 induced immune responses to a similar level as LTB-NS1, but more robust than NS1∆63 alone, particularly in the context of oral immunization of mice. Oral vaccination of LTB-NS1∆63 led to a higher survival rate than that of NS1∆63 or live-attenuated JEV vaccine SA14–14–2 in the mice receiving lethal JEV challenge. LTB-NS1∆63 protein also significantly decreases the morbidity of JEV-infected mice. In addition, passive transfer of LTB-NS1∆63-induced antisera provides a protection against JEV infection in mice. Interpretation NS1∆63 bears JEV NS1 antigenicity. Besides, LTB-NS1∆63 could serve as a novel protein-based mucosa vaccine targeting JEV and other flaviviruses. Funding This work was supported by the National Natural Science Foundation, Jiangxi Province Science and Technology Committee, Education Department of Jiangxi Province.

Keywords: encephalitis virus; jev; ltb; japanese encephalitis; ltb ns1; vaccine

Journal Title: EBioMedicine
Year Published: 2021

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