一个新的抗体靶向独特的表抗原表位上长期抑制小鼠肝炎

StephenW

Prolonged suppression of HBV in mice by a novel antibody that targets a unique epitope on hepatitis B surface antigenArticle
in
Gut · October 2015
with
21 Reads
Impact Factor: 14.66 · DOI: 10.1136/gutjnl-2014-308964

• 1st
  Ty Zhang
  
  15.28 · National Institute of Diagnostics and Vaccine
  
  
  
• 2nd
  Quan Yuan
  
  29.96 · Xiamen University
  
  
  
• 
  

• 3rd
  Jing-Hua Zhao
  
  
  
• Last
  Ning-Shao Xia
  
  
  
  

AbstractObjective:
This study aimed to investigate the therapeutic potential of monoclonal antibody (mAb) against HBV as a novel treatment approach to chronic hepatitis B (CHB) in mouse models.


Methods:
Therapeutic effects of mAbs against various epitopes on viral surface protein were evaluated in mice mimicking persistent HBV infection. The immunological mechanisms of mAb-mediated viral clearance were systematically investigated.


Results:
Among 11 tested mAbs, a novel mAb E6F6 exhibited the most striking therapeutic effects in several HBV-persistent mice. Single-dose administration of E6F6 could profoundly suppress the levels of hepatitis B surface antigen (HBsAg) and HBV DNA for several weeks in HBV-transgenic mice. E6F6 regimen efficiently prevented initial HBV infection, and reduced viral dissemination from infected hepatocytes in human-liver-chimeric mice. E6F6-based immunotherapy facilitated the restoration of anti-HBV T-cell response in hydrodynamic injection (HDI)-based HBV carrier mice. Immunological analyses suggested that the Fcγ receptor-dependent phagocytosis plays a predominant role in E6F6-mediated viral suppression. Molecular analyses suggested that E6F6 recognises an evolutionarily conserved epitope (GPCK(R)TCT) and only forms a smaller antibody-viral particle immune complex with limited interparticle crosslinking when it binds to viral particles. This unique binding characteristic of E6F6 to HBV was possibly associated with its effective in vivo opsonophagocytosis for viral clearance.


Conclusions:
These results provided new insight into understanding the therapeutic role and mechanism of antibody against persistent viral infection. The E6F6-like mAbs may provide a novel immunotherapeutic agent against human chronic HBV infection.

StephenW

乙型肝炎病毒的小鼠长期抑制由一个新的抗体靶向独特的表位上乙肝表面抗原
文章在肠道·2015年10月21读取
影响因子：14.66·DOI：10.1136 / gutjnl-2014-308964

    第一泰张
    15.28·诊断和疫苗研究所
    第二袁泉
    29.96·厦门大学

    第三景赵华
    最后宁少侠

抽象的
目的：
本研究旨在探讨单克隆抗体（mAb）对HBV的治疗潜力在小鼠模型中新的治疗方法来治疗慢性乙型肝炎（CHB）。

方法：
对单克隆抗体对病毒表面蛋白抗原决定簇不同的治疗作用小鼠模仿持续HBV感染进行了评价。的单克隆抗体介导的病毒清除的免疫学机制进行了系统的研究。

结果：
在11测试的单克隆抗体，一种新型单克隆抗体E6F6表现在几个HBV持续性小鼠的最显着的治疗效果。 E6F6的单剂量给药可能深刻地抑制B型肝炎表面抗原（HBsAg）和HBV DNA的水平数周的HBV转基因小鼠。 E6F6方案有效地防止初始HBV感染，以及在人类肝嵌合小鼠还原病毒传播从感染的肝细胞。 E6F6基免疫促进了在高压注射（HDI）抗HBV T细胞应答的恢复的基于HBV携带者的小鼠。免疫学分析表明，该Fcγ受体依赖性吞噬起着E6F6介导的抑制病毒的主导作用。分子分析表明，E6F6识别进化上保守的表位（GPCK（R）的TCT），并仅形成较小的抗体 - 病毒颗粒的免疫复合物具有有限间交联剂时其结合病毒颗粒。 E6F6对乙肝这种独特的结合特性进行了可能与它在体内有效调理吞噬的病毒清除相关。

结论：
这些结果提供了新的见解理解抗体的持久性病毒感染的治疗作用和机制。该E6F6般的单克隆抗体可提供针对人类慢性HBV感染一种新型免疫治疗剂。