中和抗体对不同类型HEV的保护机制

Hepatitis E virus (HEV) is a common cause of acute viral hepatitis worldwide. The application of HEV capsid protein recombinant antigen to the development of HEV vaccine has been proven effective, and the vaccine developed by our group has been successfully listed in 2012. HEV is mainly transmitted through the fecal-oral route, but new data suggest that HEV infection is associated with blood transfusion. Recent studies have found that HEV virus particle density in feces and serum of infected human is different. HEV exist as enveloped-HEV (eHEV) in serum yet as naked HEV in feces. However, whether the vaccine is protective in the spread by blood transfusion has not been researched. Therefore, our group investigate the neutralization of eHEV based on the cell model. Preliminary experiments show that the HEV capsid neutralizing antibodies fail to bind eHEV but are able to neutralize eHEV infection under certain conditions. This study would provide theory support for the prevention of HEV blood transfusion spreading by investigating the protective mechanism of HEV neutralizing antibodies against different types of HEV, the infection route of eHEV, validating the protective effect of HEV vaccine or neutralizing antibody on the transmission of blood transfusion based on animal infection model.

戊型肝炎病毒（HEV）是全球范围内急性病毒性肝炎的最主要的诱因之一，本申请依托单位将HEV衣壳蛋白重组颗粒性抗原应用于HEV疫苗的研发取得了良好效果，并于2012年成功上市。HEV主要通过粪口传播，但越来越多的病例表明，HEV也可以通过输血方式进行传播。近期研究发现HEV患者的粪便与血清中的HEV病毒粒子密度不同。血清中为具有包膜的eHEV，而粪便中为裸露的naked HEV。疫苗能否对HEV输血传播起到保护效果并未进行针对性的研究。在此基础上，本课题组基于体外细胞模型对eHEV的中和进行了探究，前期实验表明针对HEV衣壳蛋白的中和抗体不能够与eHEV结合但在特定条件下却能够中和eHEV的感染。本课题拟通过研究eHEV的感染途径，鉴定HEV中和抗体对不同类型HEV的保护机制，并基于动物感染模型验证HEV疫苗或中和抗体对于HEV输血传播的保护效果，为预防HEV的输血传播提供理论支持。

HEV主要经消化道传播，是全球范围内急性病毒性肝炎的最主要诱因之一，在一些发展中国家是50% 的急性病毒性肝炎病例的诱发病原。HEV主要通过粪口传播，然而在欧洲和亚洲越来越多的病例表明，HEV也可以通过输血传播。研究发现戊型肝炎患者的粪便与血清中的HEV病毒粒子密度不同，二者为不同的病毒类型。血清中为具有包膜的HEV病毒（eHEV）,而粪便中的为裸露的HEV病毒（naked HEV）。中和抗体对有包膜得HEV病毒的中和情况与中和机制尚不完全清楚。本研究通过分析不同类型的HEV病毒的感染差异，明确HEV输血传播的危害程度，探究了eHEV的感染途径及中和抗体对不同类型HEV的作用，基于疫苗免疫血清探究了疫苗对eHEV的中和作用，评估了献血人群中HEV的传播风险，阐明疫苗对于HEV输血传播产生保护的作用。