Wu Qunfeng, Fang Liurong, Wu Xuebao, Li Bin, Luo Rui, Yu Zhengjun, Jin Meilin, Chen Huanchun, Xiao Shaobo
State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan 430070, China.
Mol Immunol. 2009 Jul;46(11-12):2210-7. doi: 10.1016/j.molimm.2009.04.017. Epub 2009 May 14.
Baculovirus has emerged recently as a novel and attractive gene delivery vehicle for mammalian cells. In this study, baculovirus pseudotyped with vesicular stomatitis virus glycoprotein was used as a vector to express the hemagglutinin (HA) protein of highly pathogenic H5N1 avian influenza virus, A/Chicken/Hubei/327/2004 (HB/327). The resultant recombinant baculovirus (BV-G-HA) mediated gene delivery and HA expression efficiently in mammalian cells. Mice immunized with 1 x 10(9)PFU of BV-G-HA developed significantly higher levels of H5-specific antibodies and cellular immunity than those that received 100 microg of DNA vaccines expressing HA, and were completely protected from lethal challenge with HB/327. Different vaccination doses were further tested in chickens, and these experiments demonstrated that 1 x 10(8)PFU of BV-G-HA offered complete protection from challenge with 100 LD(50) of HB/327. These data indicate that the pseudotype baculovirus-mediated vaccine could be utilized as an alternative strategy against the pandemic spread of H5N1 influenza virus.
杆状病毒最近已成为一种用于哺乳动物细胞的新型且有吸引力的基因传递载体。在本研究中,用泡状口炎病毒糖蛋白假型化的杆状病毒被用作载体来表达高致病性H5N1禽流感病毒A/Chicken/Hubei/327/2004(HB/327)的血凝素(HA)蛋白。所得重组杆状病毒(BV-G-HA)在哺乳动物细胞中介导了高效的基因传递和HA表达。用1×10⁹ PFU的BV-G-HA免疫的小鼠产生的H5特异性抗体水平和细胞免疫显著高于接受100μg表达HA的DNA疫苗的小鼠,并且完全受到保护,免受HB/327的致死性攻击。在鸡中进一步测试了不同的疫苗接种剂量,这些实验表明1×10⁸ PFU的BV-G-HA提供了完全保护,使其免受100 LD₅₀的HB/327攻击。这些数据表明,假型杆状病毒介导的疫苗可作为对抗H5N1流感病毒大流行传播的替代策略。