Effective Chikungunya Virus-like Particle Vaccine Produced in Insect Cells
Effective Chikungunya Virus-like Particle Vaccine Produced in Insect Cells
复制标题
DOI：
10.1371/journal.pntd.0002124
复制
发表时间：
2013-03-01
影响因子：
3.8
通讯作者：
Pijlman, Gorben P.
中科院分区：
文献类型：
--
作者：
Metz, Stefan W.;Gardner, Joy;Pijlman, Gorben P.
新兴的致关节炎、蚊媒传播的基孔肯雅病毒（CHIKV）在人类中引发严重疾病，在存在伊蚊属蚊子的国家构成严重的公共卫生威胁。本研究首次描述了利用重组杆状病毒在昆虫细胞中成功生产基孔肯雅病毒样颗粒（VLPs）。这种成熟的表达系统可快速扩大到应对疫情所需的规模，并被证明非常适合加工基孔肯雅病毒糖蛋白和生产有包膜的病毒样颗粒。在此我们表明，在成年野生型基孔肯雅病毒疾病小鼠模型中，用1微克无佐剂的基孔肯雅病毒样颗粒单次免疫可诱导高滴度的中和抗体反应，并在受到留尼汪岛基孔肯雅病毒株攻击时对病毒血症和关节炎症提供完全保护。因此，利用重组杆状病毒在昆虫细胞中生产的基孔肯雅病毒样颗粒是一种新型、安全、无复制能力且有效的基孔肯雅病毒感染疫苗候选物。
The emerging arthritogenic, mosquito-borne chikungunya virus (CHIKV) causes severe disease in humans and represents a serious public health threat in countries where Aedes spp mosquitoes are present. This study describes for the first time the successful production of CHIKV virus-like particles (VLPs) in insect cells using recombinant baculoviruses. This well-established expression system is rapidly scalable to volumes required for epidemic responses and proved well suited for processing of CHIKV glycoproteins and production of enveloped VLPs. Herein we show that a single immunization with 1 mu g of non-adjuvanted CHIKV VLPs induced high titer neutralizing antibody responses and provided complete protection against viraemia and joint inflammation upon challenge with the Reunion Island CHIKV strain in an adult wild-type mouse model of CHIKV disease. CHIKV VLPs produced in insect cells using recombinant baculoviruses thus represents as a new, safe, non-replicating and effective vaccine candidate against CHIKV infections.