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
Ophtha-Lab, Department of Ophthalmology at St. Franziskus Hospital, Muenster, Germany.
Institute for Virology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
Virology. 2017 Dec;512:194-200. doi: 10.1016/j.virol.2017.09.021. Epub 2017 Oct 3.
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.
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。
