摘要
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.
摘要译文
新出现的由蚊子传播的寨卡病毒(ZIKV)菌株由于其引起小头畸形和神经系统疾病的能力而构成全球性挑战。已经提出了几种ZIKV候选疫苗,包括灭活和减毒活病毒疫苗,基于载体的疫苗,DNA和RNA疫苗。这些已被证明在小鼠和非人类灵长类动物的临床前研究中是有效的,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且有价值的工具。在这个研究中,我们使用一种新策略基于杆状病毒表达系统生产ZIKV VLP,并证明了它们作为候选疫苗的可行性。预膜(prM)和包膜(E)蛋白质在昆虫细胞中共表达并自组装成类似于ZIKV的颗粒。我们发现使用该系统可以快速,轻松地大量制备ZIKV VLP。显示VLP在免疫小鼠中具有良好的免疫原性,因为它们刺激了高水平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疫苗是安全的,用于抗ZIKV的有效和经济的候选疫苗。
Shiyu Dai[1]]Tao Zhang[1]]Yanfang Zhang[1]]Hualin Wang[1]]Fei Deng[1]]. Zika Virus Baculovirus-Expressed Virus-Like Particles Induce Neutralizing Antibodies in Mice[J]. Virologica Sinica, 2018,33(3): 213-226