Definition of a conserved immunodominant domain on hepatitis C virus E2 glycoprotein by neutralizing human monoclonal antibodies

Definition of a conserved immunodominant domain on hepatitis C virus E2 glycoprotein by neutralizing human monoclonal antibodies
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DOI:
10.1128/jvi.02475-07
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发表时间:
2008-06-01
影响因子:
5.4
通讯作者:
Foung, Steven K. H.
Foung, Steven K. H.
中科院分区:
医学2区
文献类型:
--
作者:
Keck, Zhen-Yong;Li, Ta-Kai;Foung, Steven K. H.

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开发成功的丙型肝炎病毒(HCV)疫苗需要定义不同HCV基因型之间保守的中和表位。本发明描述了五种人单克隆抗体(HMAb),其与其它抗体交叉竞争一簇重叠表位(先前指定为结构域B)。每种HMAb广泛中和表达HCV E1和E2糖蛋白的逆转录病毒假型颗粒,以及感染性嵌合基因型1a和基因型2a病毒。参与与CD81结合的E2区域内残基的丙氨酸取代表明,参与代表性抗体结合的关键E2接触残基与参与E2与CD81结合的残基相同。
Development of a successful hepatitis C virus (HCV) vaccine requires the definition of neutralization epitopes that are conserved among different HCV genotypes. Five human monoclonal antibodies (HMAbs) are described that cross-compete with other antibodies to a cluster of overlapping epitopes, previously designated domain B. Each HMAb broadly neutralizes retroviral pseudotype particles expressing HCV E1 and E2 glycoproteins, as well as the infectious chimeric genotype la and genotype 2a viruses. Alanine substitutions of residues within a region of E2 involved in binding to CD81 showed that critical E2 contact residues involved in the binding of representative antibodies are identical to those involved in the binding of E2 to CD81.