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基于抗体的阿昔洛韦耐药性眼部单纯疱疹病毒感染免疫疗法。

Antibody-based immunotherapy of aciclovir resistant ocular herpes simplex virus infections.

作者信息

Bauer Dirk, Keller Jessica, Alt Mira, Schubert Axel, Aufderhorst Ulrich Wilhelm, Palapys Vivien, Kasper Maren, Heilingloh Christiane Silke, Dittmer Ulf, Laffer Björn, Eis-Hübinger Anna Maria, Verjans Georges M, Heiligenhaus Arnd, Roggendorf Michael, Krawczyk Adalbert

机构信息

Ophtha-Lab, Department of Ophthalmology at St. Franziskus Hospital, Muenster, Germany.

Institute for Virology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.

出版信息

Virology. 2017 Dec;512:194-200. doi: 10.1016/j.virol.2017.09.021. Epub 2017 Oct 3.

Abstract

The increasing incidence of aciclovir- (ACV) resistant strains in patients with ocular herpes simplex virus (HSV) infections is a major health problem in industrialized countries. In the present study, the humanized monoclonal antibody (mAb) hu2c targeting the HSV-1/2 glycoprotein B was examined for its efficacy towards ACV-resistant infections of the eye in the mouse model of acute retinal necrosis (ARN). BALB/c mice were infected by microinjection of an ACV-resistant clinical isolate into the anterior eye chamber to induce ARN and systemically treated with mAb hu2c at 24h prior (pre-exposure prophylaxis) or at 24, 40, and 56h after infection (post-exposure immunotherapy). Mock treated controls and ACV-treated mice showed pronounced retinal damage. Mice treated with mAb hu2c were almost completely protected from developing ARN. In conclusion, mAb hu2c may become a reliable therapeutic option for drug/ACV-resistant ocular HSV infections in humans in order to prevent blindness.

摘要

在工业化国家,眼部单纯疱疹病毒(HSV)感染患者中阿昔洛韦(ACV)耐药菌株的发病率不断上升,这是一个重大的健康问题。在本研究中,针对HSV-1/2糖蛋白B的人源化单克隆抗体(mAb)hu2c在急性视网膜坏死(ARN)小鼠模型中,被检测其对眼部ACV耐药感染的疗效。通过将ACV耐药临床分离株显微注射到前房来感染BALB/c小鼠以诱导ARN,并在感染前24小时(暴露前预防)或感染后24、40和56小时(暴露后免疫治疗)用mAb hu2c进行全身治疗。模拟治疗的对照组和ACV治疗的小鼠表现出明显的视网膜损伤。用mAb hu2c治疗的小鼠几乎完全受到保护,未发生ARN。总之,为预防失明,mAb hu2c可能成为治疗人类药物/ACV耐药性眼部HSV感染的可靠治疗选择。

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