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, Hubei, China.
J Gene Med. 2009 Jan;11(1):57-65. doi: 10.1002/jgm.1271.
Japanese encephalitis (JE) is a serious infection and disease in southern and eastern Asia. The design and development of safer and more efficacious vaccines against Japanese encephalitis virus (JEV) is a high-priority target in the world. Recently, baculovirus pseudotyped with vesicular stomatitis virus glycoprotein (VSVG) was described as an attractive gene delivery vehicle in mammalian cells and a potential vector for vaccine development. In the present study, we constructed a recombinant pseudotype baculovirus encoding the 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 of 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 compared to 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)是南亚和东亚地区一种严重的感染性疾病。研发更安全、更有效的抗日本脑炎病毒(JEV)疫苗是全球的一个高度优先目标。最近,水疱性口炎病毒糖蛋白(VSVG)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以及一种潜在的疫苗开发载体。在本研究中,我们构建了一种编码JEV包膜(E)蛋白的重组假型杆状病毒,并证明其能在小鼠中引发高保护性免疫。
通过将JEV E基因片段插入pFastBac-VSV/G载体中构建重组假型杆状病毒(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,并与用灭活疫苗和编码相同JEV基因的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,与DNA疫苗相比,BV-G-E能引发更高水平的保护性免疫,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。