Filovirus-like particles produced in insect cells: Immunogenicity and protection in rodents
Filovirus-like particles produced in insect cells: Immunogenicity and protection in rodents
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DOI：
10.1086/520612
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发表时间：
2007-11-15
影响因子：
6.4
通讯作者：
Bavari, Sina
中科院分区：
文献类型：
--
作者：
Warfield, Kelly L.;Posten, Nichole A.;Bavari, Sina
背景在人293 T胚胎肾细胞中产生的埃博拉病毒（EBOV）和马尔堡病毒（MARV）的病毒样颗粒（VLP）已被证明是对抗丝状病毒感染的有效疫苗。在这项研究中，我们探索了生产基于丝状病毒样颗粒的疫苗的替代策略，以加速开发过程。这项工作的目标是增加VLP的产量，同时保留其免疫原性。通过使用表达来自共感染昆虫细胞的糖蛋白、VP 40基质蛋白和核蛋白的重组杆状病毒构建体产生埃博拉病毒和马尔堡病毒VLP（分别为eVLP和mVLP）。对杆状病毒eVLPs和mVLPs进行了生物化学表征，并进一步研究了eVLPs在昆虫细胞中产生的免疫应答。杆状病毒衍生的eVLP引起人髓样树突状细胞（DC）的成熟，表明其免疫原性。用昆虫细胞来源的eVLPs免疫小鼠产生的抗体和细胞应答与用哺乳动物293T细胞来源的eVLPs免疫的小鼠相当，并且以剂量依赖性方式保护免于EBOV攻击。总之，这些数据表明，由杆状病毒表达系统产生的丝状病毒样颗粒（其适于大规模生产）是高度免疫原性的，并且适合作为用于预防丝状病毒感染的安全有效的疫苗。
Background. Virus-like particles (VLPs) of Ebola virus (EBOV) and Marburg virus (MARV) produced in human 293T embryonic kidney cells have been shown to be effective vaccines against filoviral infection. In this study, we explored alternative strategies for production of filovirus-like particle-based vaccines, to accelerate the development process. The goal of this work was to increase the yield of VLPs, while retaining their immunogenic properties.Methods. Ebola and Marburg VLPs (eVLPs and mVLPs, respectively) were generated by use of recombinant baculovirus constructs expressing glycoprotein, VP40 matrix protein, and nucleoprotein from coinfected insect cells. The baculovirus-derived eVLPs and mVLPs were characterized biochemically, and then the immune responses produced by the eVLPs in insect cells were studied further.Results. The baculovirus-derived eVLPs elicited maturation of human myeloid dendritic cells (DCs), indicating their immunogenic properties. Mice vaccinated with insect cell-derived eVLPs generated antibody and cellular responses equivalent to those vaccinated with mammalian 293T cell-derived eVLPs and were protected from EBOV challenge in a dose-dependent manner.Conclusion. Together, these data suggest that filovirus-like particles produced by baculovirus expression systems, which are amenable to large-scale production, are highly immunogenic and are suitable as safe and effective vaccines for the prevention of filoviral infection.