预防性丙型肝炎病毒疫苗研究新策略

Novel Strategies of Prophylactic HCV Vaccine

全球有超过7 000万名丙型肝炎病毒(Hepatitis C virus,HCV)慢性感染患者,给社会带来严重的公共卫生安全问题。直接抗病毒药物(Direct antiviral drugs,DAA)能够有效地治愈慢性丙型肝炎病毒感染,但治愈后患者仍存在再感染的可能,预防性疫苗(Prophylactic vaccine)是彻底切断HCV传播的最有效途径。目前HCV预防性疫苗的研发已取得一定进展,能够诱导极少数受试者产生广谱中和抗体(Broadly neutralizing antibodies),如何在绝大多数个体中诱导保护性广谱中和抗体则是当前HCV预防性疫苗研究所面临的最大挑战。本文总结了当前疫苗免疫学的研究进展:包括抗原特异的B细胞前体(Precursor B cell)、滤泡辅助性T细胞(Follicular T helper cell,Tfh)、滤泡调节性T细胞(Follicular T regulatory cell,Tfr)、抗体重链基因1-69(VH1-69)编码抗体成熟特点;基于胚系靶向(Germline-targeting)的免疫原设计与序贯免疫策略(Sequential immunization)等,期望能为HCV疫苗研究提供新的思路。

There are more than 70 million HCV infected patients in the world,causing huge public health burden. Although direct antiviral drugs(DAA)effectively cure chronic HCV infection,HCV reinfection still is possible in cured patients. Prophylactic vaccine is the most effective way to absolutely block HCV transmission.Currently there is no available commercial HCV vaccine,although pre-clinical trials show elicited neutralizing antibody response in small percent of donors by immunization with HCV glycoprotein,which still is challenging to elicit broad neutralizing antibodies in most of donors. In this article,we reviewed current progresses in basic immunology and vaccination immunology including antigen-specific na?ve precursor B cell,follicular T helper cell(Tfh),follicular regulatory T cell(Tfr),VH immunoglobulin genes 1-69 and Sequential immunization,hoping to provide new strategies for HCV vaccine.