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过程工程学报 ›› 2022, Vol. 22 ›› Issue (4): 469-477.DOI: 10.12034/j.issn.1009-606X.221134

• 研究论文 • 上一篇    下一篇

Al-Pickering乳液提高口蹄疫疫苗热稳定性的应用

陈秋汀1,2， 吴楠2， 吴颉2*， 王晓军1*， 马光辉2
  

  1. 1. 西安工程大学环境与化学工程学院，陕西 西安 710600 2. 中国科学院过程工程研究所生化工程国家重点实验室，北京 100190
  • 收稿日期:2021-04-21 修回日期:2021-05-17 出版日期:2022-04-28 发布日期:2022-04-24
  • 通讯作者: 吴颉 wujie@ipe.ac.cn
  • 作者简介:陈秋汀(1996-)，女，陕西省汉中市人，硕士研究生，生物化工专业，E-mail: 945282191@qq.com；通讯联系人，吴颉，E-mail: wujie@ipe.ac.cn；王晓军，E-mail: 306211156@qq.com.
  • 基金资助:
    国家自然科学基金资助项目

Enhancement of the thermostability of foot-and-mouth disease vaccine via Al-Pickering emulsion

Qiuting CHEN1,2,  Nan WU2,  Jie WU2*,  Xiaojun WANG1*,  Guanghui MA2   

  1. 1. School of Environmental and Chemical Engineering, Xi΄an Polytechnic of Sciences, Xi΄an, Shaanxi 710600, China 2. State Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190, China
  • Received:2021-04-21 Revised:2021-05-17 Online:2022-04-28 Published:2022-04-24
  • Contact: WU Jie wujie@ipe.ac.cn

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摘要： 口蹄疫疫苗是一种重要的兽用疫苗，对畜牧业的发展具有重要作用。但其存在抗原热稳定性差、易失活等问题。目前，有研究者对口蹄疫病毒五聚体交界处的氨基酸改造，作为提高口蹄疫疫苗热稳定性的策略之一。然而这种方法操作复杂，要针对不同血清型病毒衣壳进行分别设计。为解决这一问题，本工作提出将抗原稳定与佐剂设计相结合的策略，构建Pickering乳液，以期提高口蹄疫疫苗的热稳定性。采用水热法制备得到了球状、棒状、片状氢氧化铝颗粒，在此基础上以角鲨烯为油相制备粒径均一的Al-Pickering乳液。随后采用差示扫描荧光法评价了灭活口蹄疫病毒(iFMDV)与Al-Pickering乳液结合后的热稳定性，结果表明各组Al-Pickering乳液对iFMDV热稳定性均有提高，其中棒状-Pickering乳液提升效果最佳，将iFMDV裂解温度提高了1.7℃。同时，动物实验结果表明Al-Pickering乳液能够增强iFMDV特异性抗体IgG分泌水平。综上，制备的Al-Pickering乳液能够稳定抗原结构并增强体液免疫水平，且制备工艺简单。该研究为提高疫苗热稳定性的佐剂研究提供了新的选择。

关键词: 灭活口蹄疫病毒疫苗, 热稳定性, Al-Pickering乳液, 氢氧化铝颗粒, 不同形貌

Abstract: Foot-and-mouth disease vaccine is a veterinary vaccine, which plays an important role in the development of animal husbandry. However, there are some problems of foot-and-mouth disease vaccines such as poor antigen thermal stability and easy inactivation of antigen. At present, researchers have modified amino acids at the junction of foot-and-mouth disease virus pentamer as one of the strategies to improve the thermal stability of foot-and-mouth disease virus vaccine. This method is complicated to operate and needs to be designed separately for different serotypes of viral capsids. Therefore, this research proposes a strategy that combines antigen stabilization with adjuvant design, combing the oli-in-water emulsion with aluminum hydroxide particles to construct a particle-stabilized emulsion (Pickering emulsion), which would improve the thermal stability of the foot-and-mouth disease vaccine. In this work, spherical, rod-shaped, and flaky aluminum hydroxide particles were prepared by hydrothermal method. The prepared aluminum hydroxide particles had good dispersion, uniform particle size distribution and high crystallinity. Due to the rough surface of Pickering emulsions, antigens were absorbed on the surface and cracks of particles. On this basis, squalene was used as oil phase to prepare Al-Pickering emulsion with uniform size. Subsequently, differential scanning fluorimetry was used to evaluate the thermal stability of inactivated foot-and-mouth disease virus (iFMDV) combined with Al-Pickering emulsion. The results showed that each group of Al-Pickering emulsions improved the thermal stability of iFMDV. The rod-Pickering emulsion had the best promotion effect, and the pyrolysis temperature of iFMDV increased by 1.7?C. The adjuvant effect of Al-Pickering was evaluated by animal experiment. Animal experiment results showed that Al-Pickering emulsion effectively activated the titer of iFMDV specific antibody IgG in serum. In summary, Al-Pickering enhanced the humoral responses and stabilized iFMDV after loading. In addition, they are easily prepared and low-cost. It provides a new idea for the research of adjuvants to improve the thermal stability of vaccines.

Key words: inactivated foot-and-mouth disease virus, thermal stability, Al-Pickering emulsion, aluminum hydroxide particles, different morphology