Department of Gastroenterology, Zhongda Hospital, Southeast University, Nanjing, Jiangsu, China.
College of Basic Medicine, Shanghai University of Medicine & Health Sciences, Shanghai, China.
Vaccine. 2019 Oct 31;37(46):6922-6930. doi: 10.1016/j.vaccine.2019.09.036. Epub 2019 Oct 8.
Design and immunogenicity assessment of the combined vaccine candidate against zoonotic hepatitis E virus (HEV) and foot-and-mouth disease virus (FMDV).
Using the molecular cloning technology, we produced and purified 9 HEV ORF2-truncated proteins (HEV genotype 4). Then, we compared their thermal stability, antigenicity, and immunogenicity to select the best HEV immunogen. Next, we used the adjuvant Montanide ISA-206 to prepare different formulations of HEV vaccine alone, FMDV vaccine alone and HEV-FMDV combined vaccine. The formulations were injected into mice and the induced humoral immune responses were monitored up 12 weeks post-immunization.
The HEV p222 protein could self-assemble into VLPs (∼34 nm) and showed higher stability and better antigenicity/immunogenicity than the other HEV antigens, thus it was selected as the best HEV immunogen. Mice immunization with the FMDV vaccine alone induced high FMDV-specific antibody titers in a dose-dependent manner; the HEV p222 protein also induced high levels of anti-HEV antibodies but in a dose-independent manner. The HEV-FMDV combination induced anti-FMDV antibody titers 7-16-fold higher than the titers induced by the FMDV vaccine alone, and HEV-specific antibody titers 2.4-fold higher than those induced by the HEV p222 antigen alone.
Herein, we proposed a new approach for the control of zoonotic HEV infection through its control in its main host (pig). We also designed the first HEV-FMDV combined vaccine and the preliminary analyses revealed a synergistic effect on the immunogenicity of both HEV and FMDV antigens.
设计和评估针对人畜共患戊型肝炎病毒(HEV)和口蹄疫病毒(FMDV)的联合疫苗候选物。
利用分子克隆技术,我们产生并纯化了 9 种 HEV ORF2 截断蛋白(HEV 基因型 4)。然后,我们比较了它们的热稳定性、抗原性和免疫原性,以选择最佳的 HEV 免疫原。接下来,我们使用佐剂 Montanide ISA-206 单独制备不同配方的 HEV 疫苗、FMDV 疫苗和 HEV-FMDV 联合疫苗。将这些配方注射到小鼠体内,监测免疫后 12 周内诱导的体液免疫反应。
HEV p222 蛋白可以自组装成 VLPs(∼34nm),比其他 HEV 抗原具有更高的稳定性和更好的抗原性/免疫原性,因此被选为最佳的 HEV 免疫原。单独用 FMDV 疫苗免疫小鼠可剂量依赖性地诱导出高滴度的 FMDV 特异性抗体;HEV p222 蛋白也诱导出高水平的抗-HEV 抗体,但呈剂量非依赖性。HEV-FMDV 联合诱导的抗-FMDV 抗体滴度比单独使用 FMDV 疫苗诱导的滴度高 7-16 倍,HEV 特异性抗体滴度比单独使用 HEV p222 抗原诱导的滴度高 2.4 倍。
本研究提出了一种通过控制主要宿主(猪)来控制人畜共患 HEV 感染的新方法。我们还设计了首个 HEV-FMDV 联合疫苗,初步分析显示对 HEV 和 FMDV 抗原的免疫原性具有协同作用。