以编码靶向 CD317 的 HBs 抗原的 DNA 疫苗进行免疫接种可在小鼠中引发增强的免疫应答。

Vaccination with a DNA vaccine encoding CD317-targeting HBs antigen elicits enhanced immunity in mice.

机构信息

Shenzhen Laboratory of Fully Human Antibody Engineering, Institute of Biomedicine and Biotechnology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055, PR China; Shenzhen College of Advanced Technology, University of Chinese Academy of Sciences, 518055, China.

出版信息

Biochem Biophys Res Commun. 2018 Oct 12;504(4):865-870. doi: 10.1016/j.bbrc.2018.09.024. Epub 2018 Sep 13.

DOI:10.1016/j.bbrc.2018.09.024

PMID:30219230

Abstract

BACKGROUND

Conventional hepatitis B virus (HBV) vaccines fail to induce protective antibody titers in 5-10% of immune-competent vaccines. Therefore, safe and effective HBV vaccines are still clinically needed.

METHODS

In this study, we developed a plasmid DNA vaccine encoding CD317 single-chain fragment variable (α317scFv) linked with the hepatitis B surface antigen (HBsAg) and detected the humoral and cellular immune responses elicited by this vaccine in BALB/c mice.

RESULTS

Vaccination with this fusion DNA vaccine in BALB/c mice induced more robust antiviral T cell and antibody immunity against HBsAg. Compared with mice vaccinated with control vaccine encoding HBsAg, the level of serum-circulating anti-HBsAg antibody (HBsAb) was nearly double in fusion DNA-vaccinated mice. More interesting, splenic lymphocytes isolated from fusion DNA-vaccinated mice showed more potent proliferation and IFN-γ production after being re-stimulated with recombinant HBsAg in vitro. And not only that, the cytotoxicity of fusion DNA vaccine-sensitized splenocytes was ∼3-fold higher than that of controls.

CONCLUSION

Taken together, our results reveal that the fusion DNA vaccine can induce more effective immunological protection against HBV, and is a promising candidate for preventing HBV infection.

摘要

背景

常规乙型肝炎病毒 (HBV) 疫苗在 5-10%的免疫功能正常人群中无法诱导保护性抗体滴度。因此，临床上仍需要安全有效的 HBV 疫苗。

方法

本研究构建了一种编码 CD317 单链片段可变区 (α317scFv) 与乙型肝炎表面抗原 (HBsAg) 融合的质粒 DNA 疫苗，并检测该疫苗在 BALB/c 小鼠中诱导的体液和细胞免疫应答。

结果

该融合 DNA 疫苗在 BALB/c 小鼠中诱导了更强大的抗病毒 T 细胞和针对 HBsAg 的抗体免疫应答。与接种对照疫苗（编码 HBsAg）的小鼠相比，融合 DNA 疫苗接种小鼠的血清循环抗 HBsAg 抗体（HBsAb）水平几乎增加了一倍。更有趣的是，从融合 DNA 疫苗接种小鼠分离的脾淋巴细胞在体外重新刺激重组 HBsAg 后显示出更强的增殖和 IFN-γ 产生。不仅如此，融合 DNA 疫苗致敏的脾细胞的细胞毒性比对照高约 3 倍。