Conley A J, Gorny M K, Kessler J A, Boots L J, Ossorio-Castro M, Koenig S, Lineberger D W, Emini E A, Williams C, Zolla-Pazner S
Department of Antiviral Research, Merck Research Laboratories, West Point, Pennsylvania 19486.
J Virol. 1994 Nov;68(11):6994-7000. doi: 10.1128/JVI.68.11.6994-7000.1994.
Human monoclonal antibody 447-52D binds to the V3 determinant of the human immunodeficiency virus type 1 (HIV-1) gp120 external glycoprotein. Its binding requires the expression of the GPxR sequence at the center of the V3 domain. HIV-1 variants that are adapted to replication in T-lymphoid cell lines and express this sequence motif are efficiently neutralized by the antibody (M. K. Gorny, A. J. Conley, S. Karwowska, A. Buchbinder, J.-Y. Xu, E. A. Emini, S. Koenig, and S. Zolla-Pazner, J. Virol. 66:7538-7542, 1992). In the present study, the antiviral activity of 447-52D was further defined with regard to its ability to mediate neutralization of primary HIV-1 clinical isolates. Again, the antibody was found to potently neutralize those isolates that expressed the binding sequence. We confirmed that this determinant is commonly expressed by virus isolates belonging to the subtype (clade) B sequence classification. As such, 447-52D may be useful for prophylactic and immunotherapeutic intervention. In addition, the study demonstrated that neutralization of primary HIV-1 isolates is possible if mediated by an appropriate antibody.
人源单克隆抗体447-52D可与人免疫缺陷病毒1型（HIV-1）包膜糖蛋白gp120的V3决定簇结合。其结合需要V3结构域中心的GPxR序列的表达。适应于在T淋巴细胞系中复制并表达该序列基序的HIV-1变体可被该抗体有效中和（M.K.戈尔尼、A.J.康利、S.卡尔沃夫斯卡、A.布赫宾德、J.-Y.徐、E.A.埃米尼、S.凯尼格和S.佐拉-帕兹纳，《病毒学杂志》66:7538-7542，1992年）。在本研究中，就447-52D介导中和原发性HIV-1临床分离株的能力而言，其抗病毒活性得到了进一步明确。同样，发现该抗体可有效中和那些表达结合序列的分离株。我们证实，该决定簇通常由属于B亚型（分支）序列分类的病毒分离株表达。因此，447-52D可能对预防性和免疫治疗干预有用。此外，该研究表明，如果由适当的抗体介导，中和原发性HIV-1分离株是可能的。
