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人乳头瘤病毒L2的一种具有保护作用且广泛交叉中和的表位

A protective and broadly cross-neutralizing epitope of human papillomavirus L2.

作者信息

Gambhira Ratish, Karanam Balasubramanyam, Jagu Subhashini, Roberts Jeffrey N, Buck Christopher B, Bossis Ioannis, Alphs Hannah, Culp Timothy, Christensen Neil D, Roden Richard B S

机构信息

Department of Pathology, The Johns Hopkins University, Baltimore, Maryland 21231, USA.

出版信息

J Virol. 2007 Dec;81(24):13927-31. doi: 10.1128/JVI.00936-07. Epub 2007 Oct 10.

Abstract

We generated a monoclonal antibody, RG-1, that binds to highly conserved L2 residues 17 to 36 and neutralizes human papillomavirus 16 (HPV16) and HPV18. Passive immunotherapy with RG-1 was protective in mice. Antiserum to the HPV16 L2 peptide comprising residues 17 to 36 (peptide 17-36) neutralized pseudoviruses HPV5, HPV6, HPV16, HPV 18, HPV31, HPV 45, HPV 52, HPV 58, bovine papillomavirus 1, and HPV11 native virions. Depletion of HPV16 L2 peptide 17-36-reactive antibodies from cross-neutralizing rabbit and human L2-specific sera abolished cross-neutralization and drastically reduced neutralization of the cognate type. This cross-neutralization of diverse HPVs associated with cervical cancer, genital warts, and epidermodysplasia verruciformis suggests the possibility of a broadly protective, peptide-based vaccine.

摘要

我们制备了一种单克隆抗体RG-1,它能与高度保守的L2蛋白第17至36位残基结合,并中和人乳头瘤病毒16型(HPV16)和HPV18。用RG-1进行的被动免疫疗法在小鼠中具有保护作用。针对包含第17至36位残基的HPV16 L2肽(肽17-36)的抗血清可中和假病毒HPV5、HPV6、HPV16、HPV18、HPV31、HPV45、HPV52、HPV58、牛乳头瘤病毒1型以及HPV11天然病毒体。从具有交叉中和作用的兔和人L2特异性血清中去除与HPV16 L2肽17-36反应的抗体,可消除交叉中和作用,并大幅降低同源型别的中和作用。这种与宫颈癌、尖锐湿疣和疣状表皮发育异常相关的多种HPV的交叉中和作用提示了基于肽的广泛保护性疫苗的可能性。

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