College of Basic Medicine, Shanghai University of Medicine & Health Sciences, 279 Zhouzhu Highway, Pudong New Area, Shanghai, 201318, China.
Department of Gastroenterology, Zhongda Hospital, Southeast University, 87 Dijiaqiao Road, Nanjing, Jiangsu Province, 210009, China.
Microb Cell Fact. 2020 Jul 11;19(1):137. doi: 10.1186/s12934-020-01394-1.
Zoonotic hepatitis E virus (HEV) infection emerged as a serious threat in the industrialized countries. The aim of this study is exploring a new approach for the control of zoonotic HEV in its main host (swine) through the design and development of an economically interesting chimeric vaccine against HEV and against a devastating swine infection: the foot-and-mouth disease virus (FMDV) infection.
First, we adopted a computational approach for rational and effective screening of the different HEV-FMDV chimeric proteins. Next, we further expressed and purified the selected chimeric immunogens in Escherichia coli (E. coli) using molecular cloning techniques. Finally, we assessed the antigenicity and immunogenicity profiles of the chimeric vaccine candidates. Following this methodology, we designed and successfully produced an HEV-FMDV chimeric vaccine candidate (Seq 8-P222) that was highly over-expressed in E. coli as a soluble protein and could self-assemble into virus-like particles. Moreover, the vaccine candidate was thermo-stable and exhibited optimal antigenicity and immunogenicity properties.
This study provides new insights into the vaccine development technology by using bioinformatics for the selection of the best candidates from larger sets prior to experimentation. It also presents the first HEV-FMDV chimeric protein produced in E. coli as a promising chimeric vaccine candidate that could participate in reducing the transmission of zoonotic HEV to humans while preventing the highly contagious foot-and-mouth disease in swine.
动物源戊型肝炎病毒 (HEV) 感染已成为工业化国家的严重威胁。本研究旨在探索一种新方法,通过设计和开发针对 HEV 和一种毁灭性猪感染(口蹄疫病毒 [FMDV] 感染)的经济有趣的嵌合疫苗来控制其主要宿主(猪)中的动物源 HEV。
首先,我们采用计算方法对不同的 HEV-FMDV 嵌合蛋白进行了合理有效的筛选。接下来,我们使用分子克隆技术进一步在大肠杆菌 (E. coli) 中表达和纯化了选定的嵌合免疫原。最后,我们评估了嵌合疫苗候选物的抗原性和免疫原性特征。按照这种方法,我们设计并成功生产了一种 HEV-FMDV 嵌合疫苗候选物(Seq 8-P222),该候选物在大肠杆菌中作为可溶性蛋白高度过表达,并能自我组装成病毒样颗粒。此外,该候选疫苗具有热稳定性,并表现出最佳的抗原性和免疫原性特性。
本研究通过使用生物信息学在实验前从更大的候选物集合中选择最佳候选物,为疫苗开发技术提供了新的见解。它还展示了第一个在大肠杆菌中生产的 HEV-FMDV 嵌合蛋白,作为一种有前途的嵌合疫苗候选物,可参与减少动物源 HEV 向人类的传播,同时预防猪的高度传染性口蹄疫。