Development of a more efficient hepatitis B virus vaccine by targeting hepatitis B virus preS to dendritic cells.
Development of a more efficient hepatitis B virus vaccine by targeting hepatitis B virus preS to dendritic cells.
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DOI：
10.1016/j.vaccine.2015.11.069
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发表时间：
2016-01
期刊：
影响因子：
5.5
通讯作者：
Mingzhen Jing;Jun Wang;Shenglin Zhu;Fang Ao;Li Wang;T. Han;Xin Yue;Ying Zhu;L. Ye;Shi Liu
中科院分区：
文献类型：
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作者：
Mingzhen Jing;Jun Wang;Shenglin Zhu;Fang Ao;Li Wang;T. Han;Xin Yue;Ying Zhu;L. Ye;Shi Liu
背景常规B肝炎病毒（HBV）疫苗不能在5-10%的免疫活性疫苗接种者中诱导保护性抗体滴度。因此，仍然迫切需要开发一种安全有效的HBV疫苗。MethodsIn这项研究中，我们开发了一种有效的和经济的方法，用于生产HBV疫苗，通过使用生物素-链霉亲和素的高结合能力。将HBV前S抗原与链霉亲和素（cSA）核心片段融合，在大肠杆菌中高效表达。我们研究了preS-cSA蛋白是否可以通过结合针对DC受体CD 205的生物素化抗体（生物素-α CD 205）靶向DC。结果preS-cSA/biotin-α CD 205复合物能靶向DC，并在体内诱导产生高滴度的抗HBV抗体IgG 2a、IgG 1和IgG。此外，用preS-cSA/生物素-α CD 205复合物接种预防雌性小鼠中的HBV感染。结论preS-cSA/biotin-α CD 205疫苗能有效地诱导机体产生抗HBV的免疫保护作用，有望成为预防HBV感染的有效疫苗。
BackgroundConventional 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.MethodsIn 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 inEscherichia 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.ResultsOur data show that the preS-cSA/biotin-αCD205 complex targeted DCs and induced high anti-HBV antibody titers of IgG2a, IgG1, and IgGin 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.ConclusionsTaken 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.