仿生矿化优化口蹄疫病毒样颗粒耐热抗逆性研究

如何提高疫苗的热稳定性、降低冷链成本是当前疫苗学的战略性问题。病毒样颗粒（VLPs）被认为是目前能够替代口蹄疫灭活疫苗的最佳候选疫苗形式，对有效防控并实现口蹄疫净化、保障畜牧业健康可持续发展具有重要社会经济意义。本研究将根据生物矿化原理，结合基因改造引入矿物成核因子，以原位矿化技术使口蹄疫病毒VLPs表面构成磷酸钙或氧化硅矿物层，通过 1）分析矿化VLPs形貌理化特性、矿化位点和结晶形式与VLPs稳定性的关系，阐明体外液态环境中矿化层对VLPs的热保护机理；2）探讨树突状细胞摄入、递呈矿化VLPs的过程，从细胞水平阐明矿化VLPs的稳定性与免疫机制的关系；3）追踪矿化VLPs在体内生物分布特性及诱导免疫反应规律，从活体水平验证生物矿化提高VLPs稳定性的免疫机制。本研究从体外、细胞及活体层面证实生物矿化赋予VLPs稳定性的机制，为VLPs疫苗及抗逆疫苗学的研究提供新的思路和理论依据。

How to improve the thermal stability and reduce the cost of the vaccine cold-chain is a strategic issue in current Vaccinology.Virus-like particles (VLPs) based-vaccine is considered as the best potential candidate for a safe and effective alternative to inactivated Foot-and-Mouth disease (FMD) vaccine. VLPs vaccine will be great significance in effective prevention and control of FMD, protection of livestock healthy and sustainable development of animal husbandry. Therefore, this study will use the combination of biomimetic mineralization principle and genetic engineering technology to introduce nucleation factor in FMD VLPs. The surface of VLPs will be enriched mineral layer of calcium phosphate or silica by using in situ mineralization technology. The study will: 1) to analyze the relationship between mineralization sites, crystal form and physical morphology of VLPs with its stability, and clarify VLPs thermal protection mechanism in liquid environment; 2) to investigate the recognition，process and presentation of mineralized VLPs process by dendritic cells, and clarify the relationship between stability and immune mechanism of mineralized VLPs in vitro; 3) to determine the characteristics of bio-distribution and the regular of immune response against mineralized VLPs in vivo, and validate the immune mechanism in which biomineralization enhances the stability of VLPs. Results from the proposed research will not only illuminate the mechanism and advantage of biomineralization VLPs from the aspect in vitro and in vivo, but will also provide scientific knowledge and new thoughts to thermostable vaccinology research.