一种具有高治疗潜力的单纯疱疹病毒通用型人重组单克隆抗体的特性分析。
Characterization of a type-common human recombinant monoclonal antibody to herpes simplex virus with high therapeutic potential.
作者信息
De Logu A, Williamson R A, Rozenshteyn R, Ramiro-Ibañez F, Simpson C D, Burton D R, Sanna P P
机构信息
Departments of Neuropharmacology, The Scripps Research Institute, La Jolla, California, USA.
出版信息
J Clin Microbiol. 1998 Nov;36(11):3198-204. doi: 10.1128/JCM.36.11.3198-3204.1998.
Abstract
We report the characterization of a type-common human recombinant monoclonal antibody previously isolated by antigen selection from a phage-displayed combinatorial antibody library established from a herpes simplex virus (HSV)-seropositive individual. Competition with well-characterized murine monoclonal antibodies and immunodetection of gD truncations revealed that this antibody recognizes the group Ib antigenic site of glycoprotein D, a highly conserved and protective type-common determinant. To our knowledge, this is the first human group Ib monoclonal antibody ever described. The antibody also displayed first-order neutralization kinetics and a high neutralization rate constant, was capable of completely inhibiting syncytium formation by a fusogenic strain of HSV type 1, and efficiently neutralized low-passage clinical isolates of both HSV serotypes. Taken together with our earlier observations of the in vivo antiviral activities of this human recombinant antibody in animal models of HSV infection, the present results support the high therapeutic potential of this antibody.
摘要
我们报告了一种类型通用的人重组单克隆抗体的特性，该抗体先前是通过抗原筛选从一名单纯疱疹病毒（HSV）血清阳性个体建立的噬菌体展示组合抗体文库中分离出来的。与特征明确的鼠单克隆抗体竞争以及对gD截短体的免疫检测表明，该抗体识别糖蛋白D的Ib组抗原位点，这是一个高度保守且具有保护作用的类型通用决定簇。据我们所知，这是有史以来描述的第一种人Ib组单克隆抗体。该抗体还表现出一级中和动力学和高中和速率常数，能够完全抑制1型HSV融合株的合胞体形成，并有效中和两种HSV血清型的低传代临床分离株。结合我们早期在HSV感染动物模型中对这种人重组抗体体内抗病毒活性的观察结果，目前的结果支持了该抗体具有很高的治疗潜力。
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