Tang Zi-Min, Tang Ming, Zhao Min, Wen Gui-Ping, Yang Fan, Cai Wei, Wang Si-Ling, Zheng Zi-Zheng, Xia Ning-Shao
State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Public Health, Xiamen University, Xiamen, Fujian 361005, PR China.
School of Life Sciences, Xiamen University, Xiamen, Fujian 361005, PR China.
Vaccine. 2015 Jul 9;33(30):3504-11. doi: 10.1016/j.vaccine.2015.05.065. Epub 2015 Jun 4.
Hepatitis E virus (HEV) is a serious public health problem that causes acute hepatitis in humans and is primarily transmitted through fecal and oral routes. The major anti-HEV antibody responses are against conformational epitopes located in a.a. 459-606 of HEV pORF2. All reported neutralization epitopes are present on the dimer domain constructed by this peptide. While looking for a neutralizing monoclonal antibody (MAb)-recognized linear epitope, we found a novel neutralizing linear epitope (L2) located in a.a. 423-437 of pORF2. Moreover, epitope L2 is proved non-immunodominant in the HEV-infection process. Using the hepatitis B virus core protein (HBc) as a carrier to display this novel linear epitope, we show herein that this epitope could induce a neutralizing antibody response against HEV in mice and could protect rhesus monkeys from HEV infection. Collectively, our results showed a novel non-immunodominant linear neutralizing epitope of hepatitis E virus, which provided additional insight of HEV vaccine.
戊型肝炎病毒(HEV)是一个严重的公共卫生问题,可导致人类急性肝炎,主要通过粪口途径传播。主要的抗HEV抗体反应针对HEV pORF2中459-606位氨基酸的构象表位。所有报道的中和表位均存在于由该肽构建的二聚体结构域上。在寻找一种可被中和性单克隆抗体(MAb)识别的线性表位时,我们发现了一个位于pORF2 423-437位氨基酸的新型中和线性表位(L2)。此外,表位L2在HEV感染过程中被证明是非免疫显性的。利用乙肝病毒核心蛋白(HBc)作为载体展示这个新型线性表位,我们在此表明该表位可在小鼠中诱导针对HEV的中和抗体反应,并可保护恒河猴免受HEV感染。总体而言,我们的结果显示了戊型肝炎病毒一个新型的非免疫显性线性中和表位,这为HEV疫苗提供了更多见解。