Li Yaoming, Ye Jing, Cao Shengbo, Xiao Shaobo, Zhao Qian, Liu Xueqin, Jin Meilin, Chen Huanchun
State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, PR China.
J Gene Med. 2009 Feb;11(2):150-9. doi: 10.1002/jgm.1282.
Japanese encephalitis (JE) is a serious infection disease throughout southern and eastern Asia. The design and development of safer and more efficacious vaccines against Japanese encephalitis virus (JEV) is a matter of high priority. Recently, baculovirus pseudotyped with vesicular stomatitis virus glycoprotein was described as an attractive gene-delivery vehicle in mammalian cells and a potential vector for vaccine development. In the present study, we constructed recombinant pseudotype baculovirus encoding the Japanese encephalitis virus (JEV) envelope (E) protein and demonstrated that it could elicit high protective immunity in mice.
Recombinant pseudotype baculovirus (BV-G-E) was generated by inserting JEV E gene fragment into pFastBac-VSV/G vector. BALB/c mice were immunized with BV-G-E and challenged with JEV wild-type strain. The neutralization antibody, interferon (IFN)-gamma expression and release, and survival rate were analysed and compared with the group of immunized with inactivated vaccine and DNA vaccine (pc-E) encoding the same gene of JEV.
We demonstrated that intramuscular injections of BV-G-E at various doses into mice produced higher levels of JEV-specific neutralizing antibodies, IFN-gamma and better protective efficacy against a lethal challenge with JEV than that of pc-E. Furthermore, BV-G-E could elicit a higher level cellular immunity response and provide equal protective efficacy against JEV challenge compared to inactivated vaccine.
Our data demonstrate that BV-G-E elicited higher levels of protective immunity than DNA vaccine and that pseudotype baculovirus-mediated gene delivery can be utilized as an alternative strategy to develop new generations of vaccines against JEV infection.
日本脑炎(JE)是一种遍及亚洲南部和东部的严重传染病。设计和开发更安全、更有效的抗日本脑炎病毒(JEV)疫苗是当务之急。最近,用水泡性口炎病毒糖蛋白假型化的杆状病毒被描述为一种在哺乳动物细胞中具有吸引力的基因递送载体和一种潜在的疫苗开发载体。在本研究中,我们构建了编码日本脑炎病毒(JEV)包膜(E)蛋白的重组假型杆状病毒,并证明其可在小鼠中引发高度保护性免疫。
通过将JEV E基因片段插入pFastBac-VSV/G载体中产生重组假型杆状病毒(BV-G-E)。用BV-G-E免疫BALB/c小鼠,并用JEV野生型毒株进行攻击。分析中和抗体、干扰素(IFN)-γ的表达和释放以及存活率,并与用编码相同JEV基因的灭活疫苗和DNA疫苗(pc-E)免疫的组进行比较。
我们证明,向小鼠肌肉注射不同剂量的BV-G-E可产生更高水平的JEV特异性中和抗体、IFN-γ,并且对JEV致死性攻击的保护效果优于pc-E。此外,与灭活疫苗相比,BV-G-E可引发更高水平的细胞免疫反应,并对JEV攻击提供同等的保护效果。
我们的数据表明,BV-G-E引发的保护性免疫水平高于DNA疫苗,并且假型杆状病毒介导的基因递送可作为开发新一代抗JEV感染疫苗的替代策略。