Novel Japanese encephalitis virus NS1-based vaccine: Truncated NS1 fused with E. coli heat labile enterotoxin B subunit
Jiawu Wan,
Ting Wang,
Jing Xu,
Tao Ouyang,
Qianruo Wang,
Yanni Zhang,
Shiqi Weng,
Yihan Li,
Yu Wang,
Xiu Xin,
Xiaoling Wang,
Sha Li,
Lingbao Kong
Affiliations
Jiawu Wan
Institute of Pathogenic Microorganism and College of Bioscience and Engineering, Jiangxi Agricultural University, Nanchang, Jiangxi, China
Ting Wang
Institute of Pathogenic Microorganism and College of Bioscience and Engineering, Jiangxi Agricultural University, Nanchang, Jiangxi, China
Jing Xu
Institute of Pathogenic Microorganism and College of Bioscience and Engineering, Jiangxi Agricultural University, Nanchang, Jiangxi, China
Tao Ouyang
Institute of Pathogenic Microorganism and College of Bioscience and Engineering, Jiangxi Agricultural University, Nanchang, Jiangxi, China
Qianruo Wang
Institute of Pathogenic Microorganism and College of Bioscience and Engineering, Jiangxi Agricultural University, Nanchang, Jiangxi, China
Yanni Zhang
Jiangxi Province Center for Disease Control and Prevention, Nanchang, Jiangxi, China
Shiqi Weng
Institute of Pathogenic Microorganism and College of Bioscience and Engineering, Jiangxi Agricultural University, Nanchang, Jiangxi, China
Yihan Li
Institute of Pathogenic Microorganism and College of Bioscience and Engineering, Jiangxi Agricultural University, Nanchang, Jiangxi, China
Yu Wang
Institute of Pathogenic Microorganism and College of Bioscience and Engineering, Jiangxi Agricultural University, Nanchang, Jiangxi, China
Xiu Xin
Institute of Pathogenic Microorganism and College of Bioscience and Engineering, Jiangxi Agricultural University, Nanchang, Jiangxi, China
Xiaoling Wang
Institute of Pathogenic Microorganism and College of Bioscience and Engineering, Jiangxi Agricultural University, Nanchang, Jiangxi, China
Sha Li
Institute of Pathogenic Microorganism and College of Bioscience and Engineering, Jiangxi Agricultural University, Nanchang, Jiangxi, China; Corresponding authors.
Lingbao Kong
Institute of Pathogenic Microorganism and College of Bioscience and Engineering, Jiangxi Agricultural University, Nanchang, Jiangxi, China; Corresponding authors.
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.
