一个人类单克隆抗体，抗乙肝病毒具有强效中和作用的小包

StephenW

MAbs. 2015 Dec 29:0. [Epub ahead of print]
A human monoclonal antibody against small envelope protein of hepatitis B virus with potent neutralization effect.Wang W1, Sun L2, Li T1, Ma Y3, Li J4, Liu Y2, Li M1, Wang L1, Li C2, Xie Y1, Wen Y1, Liang M2, Chen L1, Tong S1.
Author information

• 1a Department of Pathobiology and Key Laboratory of Medical Molecular Virology , School of Basic Medical Sciences, Fudan University , Shanghai , China.
• 2b Key Laboratory for Medical Virology, NHFPC, National Institute for Viral Disease Control and Prevention , China CDC.
• 3c Putuo District Center Hospital, Shanghai University of Traditional Chinese Medicine , Shanghai , China.
• 4d Liver Research Center, The Warren Alpert School of Medicine, Brown University , Providence , Rhode Island , USA .
  

AbstractHepatitis B virus (HBV) produces large (L), middle (M), and small (S) envelope proteins, alternatively referred to as hepatitis B surface antigen (HBsAg). Currently, yeast-derived S protein serves as the preventive vaccine, while hepatitis B immune globulin (HBIG) concentrated from pooled plasma of vaccine recipients is employed for post-exposure prophylaxis. However, only a small proportion of the antibodies in HBIG are HBV specific. In the present study, a human monoclonal anti-S antibody (G12) was developed, produced under GLP conditions, and subjected to a panel of functional assays. In vitro results demonstrated high affinity of G12 for the S protein (KD=7.56 nM). It reacted with envelope proteins of all 7 HBV genotypes tested (A-F, H) by immunofluorescent staining, and more than 97% of HBsAg-positive patient serum samples by enzyme-linked immunosorbent assay. G12 recognized a conformational epitope, although the exact sequence remains unknown. Strikingly, G12 was at least 1,000-fold more potent than HBIG in neutralizing HBV infectivity in both HepaRG cell line and HepG2 cells reconstituted with the HBV receptor. In a transgenic mouse model of HBV persistence, a single peritoneal injection of G12 markedly diminished serum HBsAg titers in all seven mice, which was sustained for the observation period of 144 days in mice with low pre-treatment levels. While the therapeutic potential of G12 warrants further investigation using a large number of animals, G12 is a potent neutralizing human monoclonal antibody and a promising candidate to replace or supplement HBIG in the prevention of HBV infection.


KEYWORDS: Anti-S; hepatitis B immune globulin; hepatitis B virus; human monoclonal antibody; neutralization; small envelope protein; transgenic mice

StephenW

单克隆抗体。 2015年12月29日：0。 [打印EPUB提前]
一个人类单克隆抗体，抗乙肝病毒具有强效中和作用的小包膜蛋白。
王W1，孙L2，李T1，马Y3，李J4，刘Y2，李M1，王L1，C2李，谢Y1，文Y1，梁M2，陈L1，通S1。
作者信息

    病理生物学1A系医学分子病毒学的基础医学院，复旦大学，上海，中国和重点实验室。
    2B重点实验室医学病毒学，NHFPC，国立病毒病预防控制，中国疾控中心。
    3C普陀区中心医院，中国传统医药，上海，中国的上海大学。
    4D肝病研究中心，医学院，布朗大学，普罗维登斯，罗得岛州，美国的沃伦·阿尔珀特学校。

抽象

乙型肝炎病毒（HBV）产生大（L），中（M）和小的（S） - 包膜蛋白，可选地称为B型肝炎表面抗原（HBsAg）。目前，酵母产生的S蛋白作为预防性疫苗，而乙肝免疫球蛋白（HBIG）从浓缩疫苗接种者的混合血浆被用于暴露后预防。然而，在HBIG的抗体的只有一小部分是乙肝病毒特异性的。在本研究中，人单克隆抗-S抗体（G12）的开发，GLP条件下产生，并进行功能性测定中面板。体外实验结果表明G12的S蛋白（KD = 7.56 nm）的高亲和力。它下与测试的所有7 HBV基因型（AF，H）通过免疫荧光染色的包膜蛋白和HBsAg阳性患者血清样品通过酶联免疫吸附试验的97％以上。 G12认可的构象表位，但确切的序列仍然未知。引人注目的是，G12至少是1000倍，比HBIG更有效中和HBV感染两种HepaRG细胞株和HepG2细胞重组与乙肝病毒受体。乙肝病毒的持久性的转基因小鼠模型中，单个腹腔注射G12的显着减少在所有七只小鼠，将其持续144天的小鼠具有低治疗前水平的观察期血清HBsAg滴度。而G12权证的治疗潜力进一步调查使用大量动物，G12是一种有效的中和性人单克隆抗体和有希望的候选替换或预防HBV感染的补充HBIG。
关键词：

抗-S;乙肝免疫球蛋白;乙型肝炎病毒;人单克隆抗体;中和;小包膜蛋白;转基因小鼠

MP4

nn年前就能做的事情，却全球都没一直没能面市

StephenW

MP4 发表于 2015-12-31 17:29
nn年前就能做的事情，却全球都没一直没能面市

是的，乙肝表面抗原单克隆抗体很大的期望。他们发现乙肝表面抗原，乙肝表面抗体免疫复合物是有害肾的. FDA要求一个非常广泛的3期临床试验，以将其用作HBV的预防药物在肝脏移植.
我希望他们能重新调查乙肝表面抗原单克隆抗体的治疗潜力.