Jing Mingzhen, Wang Jun, Zhu Shengli, Ao Fang, Wang Li, Han Tao, Yue Xin, Zhu Ying, Ye Linbai, Liu Shi
State Key Laboratory of Virology and College of Life Sciences, Wuhan University, Wuhan 430072, China.
State Key Laboratory of Virology and College of Life Sciences, Wuhan University, Wuhan 430072, China; Clinical Research Center, Wuhan Children's Hospital, Wuhan 430016, China.
Vaccine. 2016 Jan 20;34(4):516-522. doi: 10.1016/j.vaccine.2015.11.069. Epub 2015 Dec 12.
Conventional hepatitis B virus (HBV) vaccines fail to induce protective antibody titers in 5-10% of immune-competent vaccinees. Therefore, there remains an urgent need to develop a safe and effective HBV vaccine.
In this study, we developed an effective and economical method for producing the HBV vaccine by using the high binding capacity of biotin-streptavidin. The preS antigen of HBV was fused with the core streptavidin (cSA) moiety (preS-cSA) and highly expressed in Escherichia coli. We investigated whether the preS-cSA protein could target dendritic cells (DCs) by binding a biotinylated antibody against the DC receptor CD205 (biotin-αCD205). Moreover, we evaluated the preS-cSA/biotin-αCD205 complex as a candidate vaccine by detecting the humoral and cellular immune responses elicited by this vaccine.
Our data show that the preS-cSA/biotin-αCD205 complex targeted DCs and induced high anti-HBV antibody titers of IgG2a, IgG1, and IgG in vivo. Furthermore, vaccination with the preS-cSA/biotin-αCD205 complex prevented HBV infection in female mice. More interestingly, this novel vaccine exerted a therapeutic role in mice with HBV infection.
Taken together, our results reveal that the preS-cSA/biotin-αCD205 vaccine induces effective immunological protection against HBV, and is a promising candidate for preventing HBV infections.
传统的乙型肝炎病毒(HBV)疫苗在5%-10%的免疫功能正常的接种者中无法诱导出保护性抗体滴度。因此,迫切需要开发一种安全有效的HBV疫苗。
在本研究中,我们利用生物素-链霉亲和素的高结合能力,开发了一种生产HBV疫苗的有效且经济的方法。将HBV的前S抗原与核心链霉亲和素(cSA)部分融合(preS-cSA),并在大肠杆菌中高效表达。我们研究了preS-cSA蛋白是否能通过结合抗树突状细胞(DC)受体CD205的生物素化抗体(生物素-αCD205)靶向DC。此外,我们通过检测该疫苗引发的体液和细胞免疫反应,评估preS-cSA/生物素-αCD205复合物作为候选疫苗的效果。
我们的数据表明,preS-cSA/生物素-αCD205复合物靶向DC,并在体内诱导出高滴度的IgG2a、IgG1和IgG抗HBV抗体。此外,用preS-cSA/生物素-αCD205复合物接种疫苗可预防雌性小鼠感染HBV。更有趣的是,这种新型疫苗在感染HBV的小鼠中发挥了治疗作用。
综上所述,我们的结果表明,preS-cSA/生物素-αCD205疫苗可诱导针对HBV的有效免疫保护作用,是预防HBV感染的一个有前景的候选疫苗。