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兰州兽医研究所在耐热口蹄疫病毒样颗粒疫苗研究中取得进展

2019-12-24 08:26:00 来源:兰州兽医研究所

  近日,中国农业科学院兰州兽医研究所兽用纳米材料与应用课题组在前期突破口蹄疫病毒样颗粒(VLPs)关键技术及产品工艺的基础上,进一步利用生物矿化的概念和技术,研制出耐热口蹄疫VLPs疫苗,使常规口蹄疫VLPs能够在室温中长时间保存,克服了VLPs疫苗的冷链需求限制,开辟了VLPs疫苗换代产品的新阶段。相关研究成果以“Biomineralization improved the thermostability of foot-and-mouth disease virus-like particles and protective immune response”为题,作为封面文章发表在工程技术1区期刊《Nanoscale》上。 

     

 

  Nanoscale, 2019,11, 22748-22761 https://doi.org/10.1039/C9NR05549E 

  疫苗接种是人类发展出来的对抗传染病最有效的医疗干预手段之一,但大部分疫苗对温度的敏感性,决定其从生产、贮存、运输到使用的整个过程必需冷链条件来确保其质量,而长期、稳定的低温环境的维持在现实中尤为困难且费用昂贵。因此,疫苗的耐热性优化具有重要的社会和经济意义,开发不受冷链约束的常温疫苗成为当前疫苗学关注的战略性问题,也被世界卫生组织及比尔.盖茨基金会列为全球人类健康的巨大挑战之一。 

  本研究利用仿生矿化的原理对口蹄疫VLPs进行生物矿化修饰,在VLPs表面形成钙矿化层。极端耐热性试验显示,矿化层显著提高了VLPs的耐热性,而且37℃放置7天的矿化VLPs和4℃保存的矿化VLPs诱发的免疫反应相当。此外,研究从抗原递呈角度揭示了矿化VLPs能更高效的被免疫细胞摄取,并诱导树突状细胞的成熟,进一步活化T细胞使其分化。在本研究基础上,兽用纳米材料及应用课题组已将此矿化思路和技术进一步推广到常规灭活疫苗的研发中,并已获得相关国内国际专利,不仅为获得口蹄疫系列耐热疫苗提供更多选择,更为获得稳定的新型优势疫苗提供了参考。 

     

 

  博士研究生杜平和硕士研究生刘绒欢为论文的第一作者,刘在新研究员和郭慧琛研究员为论文的通讯作者,该项研究得到了国家自然基金(31672592)、国家重点研究和发展计划专项(2017YFD0500900,2017YFD0501100,2016YFE0204100)、中央公益性科研机构基础研究基金(1610312016002,1610312018003, Y2017JC57)及中国农业科学院青年英才计划的资助。 

  原文摘要: 

  Biomineralization improves the thermostability of foot-and-mouth disease virus-like particles and the protective immune response induced 

  Ping Du,?a Ronghuan Liu,?a Shiqi Sun,a Hu Dong,a Ruibo Zhao,b Ruikang Tang, b Jianwu Dai, c Hong Yin,a Jianxun Luo,a Zaixin Liu*a and Huichen Guo *a 

  Virus-like particles (VLPs) are an ideal substitute for traditionally inactivated or attenuated viruses invaccine 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. 

  文章链接:https://pubs.rsc.org/en/content/articlelanding/2019/nr/c9nr05549e#!divAbstract 

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