State Key Laboratory of Veterinary Etiological Biology and Key Laboratory of Animal Virology of Ministry of Agriculture, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Xujiaping 1, Lanzhou, Gansu 730046, P.R. China.
Qiushi Academy for Advanced Studies, Zhejiang University, Hangzhou 310027, P.R. China.
Nanoscale. 2019 Dec 21;11(47):22748-22761. doi: 10.1039/c9nr05549e. Epub 2019 Oct 10.
Virus-like particles (VLPs) are an ideal substitute for traditionally inactivated or attenuated viruses in vaccine production. However, given the properties of their native proteins, the thermal stability of VLPs is poor. In this study, calcium mineralization was used to fabricate foot-and-mouth disease virus (FMDV) VLPs as immunogenic core-shell particles with improved thermal stability. The biomineralized VLPs were stably stored at 24 °C and 37 °C for 13 and 11 days, respectively. Animal experiments showed that the biomineralized VLPs induced specific protective immunogenic effects, even after storage at 37 °C for 7 days. The biomineralized VLPs also effectively activated dendritic cells (DCs) to express high levels of surface MHC-II, costimulatory molecules, and proinflammatory cytokines. The DCs activated by the mineralized VLPs rapidly localized to the secondary lymphoid tissues and promoted the activation of the native T-cell population. These results suggest that the biomineralization of VLPs is an effective approach to vaccine production insofar as the mineralized shell provides an adjuvant effect which improves the immunogenicity of the VLPs. Biomineralization can also confer superior heat resistance on VLPs, an advantage in vaccine production. The successful development of thermally stable, biomineralized VLPs will reduce our dependence on cold storage and delivery.
病毒样颗粒 (VLPs) 是疫苗生产中替代传统灭活或减毒病毒的理想选择。然而,鉴于其天然蛋白的特性,VLPs 的热稳定性较差。在这项研究中,利用钙矿化作用来制备口蹄疫病毒 (FMDV) VLP,使其成为具有改善热稳定性的免疫原性核壳颗粒。生物矿化的 VLP 可以分别在 24°C 和 37°C 下稳定储存 13 天和 11 天。动物实验表明,即使在 37°C 下储存 7 天,生物矿化的 VLP 也能诱导特异性的保护免疫原性效应。生物矿化的 VLP 还能有效激活树突状细胞 (DC),使其高水平表达表面 MHC-II、共刺激分子和促炎细胞因子。被矿化 VLP 激活的 DC 迅速定位到次级淋巴组织,并促进天然 T 细胞群体的激活。这些结果表明,VLPs 的生物矿化是疫苗生产的一种有效方法,因为矿化壳提供了一种佐剂效应,可提高 VLP 的免疫原性。生物矿化还可以赋予 VLP 更高的耐热性,这在疫苗生产中是一个优势。成功开发出热稳定的、生物矿化的 VLP 将减少我们对冷藏和运输的依赖。