寨卡病毒杆状病毒表达的病毒样颗粒在小鼠中诱导产生中和抗体。
Zika Virus Baculovirus-Expressed Virus-Like Particles Induce Neutralizing Antibodies in Mice.
机构信息
State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, 430071, China.
出版信息
Virol Sin. 2018 Jun;33(3):213-226. doi: 10.1007/s12250-018-0030-5. Epub 2018 May 17.
The newly emerged mosquito-borne Zika virus (ZIKV) strains pose a global challenge owing to its ability to cause microcephaly and neurological disorders. Several ZIKV vaccine candidates have been proposed, including inactivated and live attenuated virus vaccines, vector-based vaccines, DNA and RNA vaccines. These have been shown to be efficacious in preclinical studies in mice and nonhuman primates, but their use will potentially be a threat to immunocompromised individuals and pregnant women. Virus-like particles (VLPs) are empty particles composed merely of viral proteins, which can serve as a safe and valuable tool for clinical prevention and treatment strategies. In this study, we used a new strategy to produce ZIKV VLPs based on the baculovirus expression system and demonstrated the feasibility of their use as a vaccine candidate. The pre-membrane (prM) and envelope (E) proteins were co-expressed in insect cells and self-assembled into particles similar to ZIKV. We found that the ZIKV VLPs could be quickly and easily prepared in large quantities using this system. The VLPs were shown to have good immunogenicity in immunized mice, as they stimulated high levels of virus neutralizing antibody titers, ZIKV-specific IgG titers and potent memory T cell responses. Thus, the baculovirus-based ZIKV VLP vaccine is a safe, effective and economical vaccine candidate for use against ZIKV.
新出现的蚊媒寨卡病毒(ZIKV)株由于能够引起小头畸形和神经紊乱,对全球构成挑战。已经提出了几种 ZIKV 疫苗候选物,包括灭活和减毒活病毒疫苗、基于载体的疫苗、DNA 和 RNA 疫苗。这些疫苗在小鼠和非人类灵长类动物的临床前研究中已被证明是有效的,但它们的使用可能对免疫功能低下的个体和孕妇构成威胁。病毒样颗粒(VLPs)是仅由病毒蛋白组成的空颗粒,可作为临床预防和治疗策略的安全有价值的工具。在本研究中,我们使用基于杆状病毒表达系统的新策略来生产 ZIKV VLPs,并证明了它们作为疫苗候选物的使用可行性。在昆虫细胞中共同表达前膜(prM)和包膜(E)蛋白,并自组装成类似于 ZIKV 的颗粒。我们发现,该系统可快速简便地大量制备 ZIKV VLPs。VLPs 在免疫小鼠中显示出良好的免疫原性,因为它们刺激了高滴度的病毒中和抗体滴度、ZIKV 特异性 IgG 滴度和有效的记忆 T 细胞反应。因此,基于杆状病毒的 ZIKV VLP 疫苗是一种安全、有效和经济的 ZIKV 疫苗候选物。