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[1]徐灵杰,罗文新*,张 娟,等.一株乙型肝炎病毒鼠单抗的人源化及生物学活性鉴定[J].厦门大学学报(自然科学版),2017,56(01):72-78.[doi:10.6043/j.issn.0438-0479.201603029]
 XU Lingjie,LUO Wenxin*,ZHANG Juan,et al.Humanization of Therapeutic Antibody of One Hepatitis B Virus and Identification of Its Biological Activity[J].Journal of Xiamen University(Natural Science),2017,56(01):72-78.[doi:10.6043/j.issn.0438-0479.201603029]
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一株乙型肝炎病毒鼠单抗的人源化及生物学活性鉴定(PDF)
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《厦门大学学报(自然科学版)》[ISSN:0438-0479/CN:35-1070/N]

卷:
56卷
期数:
2017年01期
页码:
72-78
栏目:
研究论文
出版日期:
2017-01-23

文章信息/Info

Title:
Humanization of Therapeutic Antibody of One Hepatitis B Virus and Identification of Its Biological Activity
文章编号:
0438-0479(2017)01-0072-07
作者:
徐灵杰1罗文新1*张 娟1周 兵2张天英1胡耀凯1袁 权2夏宁邵1
1.厦门大学 生命科学学院 国家传染病诊断试剂及疫苗工程技术研究中心,2.厦门大学公共卫生学院,福建 厦门 361102
Author(s):
XU Lingjie1LUO Wenxin1*ZHANG Juan1ZHOU Bing2ZHANG Tianying1HU Yaokai1YUAN Quan2XIA Ningshao1
1.National Institute of Diagnostics and Vaccine Development in Infectious Disease,School of Life Sciences,Xiamen University,2.School of Public Health,Xiamen University,Xiamen 361102,China
关键词:
乙型肝炎病毒 噬菌体抗体库 抗体人源化 抗体药物
Keywords:
hepatitis B virus(HBV) phage display antibody library antibody humanization antibody-based drug
分类号:
Q 511
DOI:
10.6043/j.issn.0438-0479.201603029
文献标志码:
A
摘要:
乙型肝炎病毒(HBV)感染是全球最为重要的公共卫生问题之一,目前临床上治疗HBV的药物在彻底清除病毒方面并没有取得满意的结果,因此迫切需要发展能有效清除病毒,尤其是能有效清除乙肝表面抗原(HBsAg)或大幅度降低HBsAg血清学水平的创新性治疗药物.筛选到一株针对HBV和HBsAg上一个特定表位的鼠单抗129G1,它能持续有效地清除转基因小鼠体内的HBV及HBsAg,有发展为治疗性抗体药物的潜力.为了降低129G1的免疫原性,采用互补决定区(CDR)移植的方式,利用噬菌体抗体库技术对这个鼠单抗进行了人源化,最终得到人源化抗体.人源化抗体与HBsAg的结合活性与嵌合抗体相当,抗体质量浓度为1.45 μg/mL时介导THP-1细胞吞噬率达到50%.在HBV转基因小鼠的实验中,获得的129G1人源化抗体能持续有效地抑制血清中HBV DNA及清除HBsAg.
Abstract:
Hepatitis B virus(HBV)infection is a major global health problem.However,current treatments are not satisfactory in removing virus thoroughly from patients,thus we need innovative treatment strategies to remove virus continuously,especially in suppressing the levels of HBsAg and HBV DNA in vivo profoundly and persistently.In this study we discovered 129G1 mAb,which is a mouse monoclonal antibody binding to a special epitope on the hepatitis B surface(HBsAg).129G1 mAb can suppress the levels of HBsAg and HBV DNA in vivo profoundly and persistently,thus has the potential to be used in drugs of therapeutic antibodies.In order to reduce the immunogenicity of 129G1 mAb,we accomplished the humanization of 129G1 using complementarity determining region(CDR)-grafting and framework region optimization to keep the original biological function with phage display technology.129G1 humanized antibodies’ binding activity with HBsAg is similar to 129G1 cAb.It makes the phagocytosis rate of THP-1 cells up to 50% at concentration of 1.45 μg/mL.In HBV transgenic mice,the humanized 129G1 exhibited continuous ability in suppressing the HBV DNA in serum and clearing HBsAg.

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备注/Memo

备注/Memo:
收稿日期:2016-03-16 录用日期:2016-05-04
基金项目:国家自然科学基金(81371819,81571990); 福建省自然科学基金(2015J06018)
*通信作者:wxluo@xmu.edu.cn
更新日期/Last Update: 1900-01-01