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

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: Flavivirus; JEV; LTB; Mucosa vaccine; Truncated NS1.