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通过电穿孔接种DNA疫苗的小鼠中的非细胞溶解性抗原清除

Non-cytolytic antigen clearance in DNA-vaccinated mice with electroporation.

作者信息

Peng Jin-liang, Zhao Yong-gang, Mai Jun-hua, Pang Wen-ka, Guo Wei, Chen Guang-ming, Mo Guo-yu, Rao Gui-rong, Xu Yu-hong

机构信息

Schools of Life Sciences and Technology, Shanghai Jiao Tong University, Shanghai 200240, China.

出版信息

Acta Pharmacol Sin. 2007 Jul;28(7):1024-30. doi: 10.1111/j.1745-7254.2007.00591.x.

Abstract

AIM

To explore the potential of electroporation (EP)-mediated hepatitis B virus (HBV) DNA vaccination for the treatment of chronic HBV infection.

METHODS

BALB/c mice were vaccinated with HBV DNA vaccine encoding for the HBV preS(2)-S antigen, combined with or without EP. HBV surface antigen expression plasmid was administered into mice liver via a hydrodynamic injection to mimic HBV infection. The clearance of antigen in the serum and liver was detected by ELISA assay and immunohistochemical staining. The histopathology of the liver tissues was examined by HE staining and serum alanine aminotransferase assay.

RESULTS

The immunogenicity of HBV DNA vaccine encoding for the HBV preS(2)- S antigen can be improved by EP-mediated vaccine delivery. The elicited immune responses can indeed reduce the expression of HBV surface antigen (HBsAg) in hepatocytes of the mouse model that was transfected to express HBsAg using the hydrodynamic injection method. The antigen clearance process did not cause significant toxicity to liver tissue, suggesting a non-cytolytic mechanism.

CONCLUSION

The EP-aided DNA vaccination may have potential in mediating viral clearance in chronic hepatitis B patients.

摘要

目的

探讨电穿孔(EP)介导的乙型肝炎病毒(HBV)DNA疫苗治疗慢性HBV感染的潜力。

方法

用编码HBV preS(2)-S抗原的HBV DNA疫苗对BALB/c小鼠进行接种,接种时联合或不联合EP。通过流体动力学注射将HBV表面抗原表达质粒注入小鼠肝脏以模拟HBV感染。采用ELISA检测和免疫组化染色法检测血清和肝脏中抗原的清除情况。通过HE染色和血清丙氨酸氨基转移酶检测对肝组织进行组织病理学检查。

结果

EP介导的疫苗递送可提高编码HBV preS(2)-S抗原的HBV DNA疫苗的免疫原性。所引发的免疫反应确实可降低通过流体动力学注射法转染以表达HBsAg的小鼠模型肝细胞中HBV表面抗原(HBsAg)的表达。抗原清除过程未对肝组织造成明显毒性,提示存在非细胞溶解机制。

结论

EP辅助的DNA疫苗接种可能在介导慢性乙型肝炎患者病毒清除方面具有潜力。

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