期刊
EBIOMEDICINE
卷 67, 期 -, 页码 -出版社
ELSEVIER
DOI: 10.1016/j.ebiom.2021.103353
关键词
Flavivirus; JEV; Truncated NS1; LTB; Mucosa vaccine
资金
- National Natural Science Foundation of China [31460667, 31860038, 31960699]
- Jiangxi Province [20161BBF60084, GJJ180239, GJJ200405]
LTB-NS1(Delta)(63) demonstrates strong immunogenicity and shows promising results as an oral vaccine in mice. This protein-based mucosa vaccine could serve as a novel approach to combat Japanese encephalitis virus and other flaviviruses effectively.
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(Delta)(63)) with a truncated NS1 protein (NS1(Delta)(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(Delta)(63 )was assessed by determining its toxicity in vitro and in vivo. Protective capability of LTB-NS1(Delta)(63) and its-induced antisera was evaluated in the mice challenged with JEV by analyzing mortality and morbidity. Findings: LTB-NS1(Delta)(63) induced immune responses to a similar level as LTB-NS1, but more robust than NS1(Delta)(63) alone, particularly in the context of oral immunization of mice. Oral vaccination of LTB-NS1(Delta)(63) led to a higher survival rate than that of NS1(Delta)(63) or live-attenuated JEV vaccine SA14-14-2 in the mice receiving lethal JEV challenge. LTB-NS1(Delta)(63) protein also significantly decreases the morbidity of JEV-infected mice. In addition, passive transfer of LTB-NS1(Delta)(63)-induced antisera provides a protection against JEV infection in mice. Interpretation: NS1(Delta)(63) bears JEV NS1 antigenicity. Besides, LTB-NS1(Delta)(63) could serve as a novel protein-based mucosa vaccine targeting JEV and other flaviviruses. (C) 2021 The Author(s). Published by Elsevier B.V.
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