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

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

doi:10.1016/j.virol.2017.09.021

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

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

Institute of Virology

Research output: Contribution to journal › Article › peer-review

13 Scopus citations

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 24 h prior (pre-exposure prophylaxis) or at 24, 40, and 56 h 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.

Original language	English
Pages (from-to)	194-200
Number of pages	7
Journal	Virology
Volume	512
DOIs	https://doi.org/10.1016/j.virol.2017.09.021
State	Published - Dec 2017

Keywords

ARN
Aciclovir resistance
HSV
Humanized Anti-HSV-antibody
Infection of the eye

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10.1016/j.virol.2017.09.021

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Bauer, D., Keller, J., Alt, M., Schubert, A., Aufderhorst, U. W., Palapys, V., Kasper, M., Heilingloh, C. S., Dittmer, U., Laffer, B., Eis-Hübinger, A. M., Verjans, G. M., Heiligenhaus, A., Roggendorf, M., & Krawczyk, A. (2017). Antibody-based immunotherapy of aciclovir resistant ocular herpes simplex virus infections. Virology, 512, 194-200. https://doi.org/10.1016/j.virol.2017.09.021

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title = "Antibody-based immunotherapy of aciclovir resistant ocular herpes simplex virus infections",

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 24 h prior (pre-exposure prophylaxis) or at 24, 40, and 56 h 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.",

keywords = "ARN, Aciclovir resistance, HSV, Humanized Anti-HSV-antibody, Infection of the eye",

author = "Dirk Bauer and Jessica Keller and Mira Alt and Axel Schubert and Aufderhorst, {Ulrich Wilhelm} and Vivien Palapys and Maren Kasper and Heilingloh, {Christiane Silke} and Ulf Dittmer and Bj{\"o}rn Laffer and Eis-H{\"u}binger, {Anna Maria} and Verjans, {Georges M.} and Arnd Heiligenhaus and Michael Roggendorf and Adalbert Krawczyk",

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year = "2017",

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doi = "10.1016/j.virol.2017.09.021",

language = "English",

volume = "512",

pages = "194--200",

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Bauer, D, Keller, J, Alt, M, Schubert, A, Aufderhorst, UW, Palapys, V, Kasper, M, Heilingloh, CS, Dittmer, U, Laffer, B, Eis-Hübinger, AM, Verjans, GM, Heiligenhaus, A, Roggendorf, M & Krawczyk, A 2017, 'Antibody-based immunotherapy of aciclovir resistant ocular herpes simplex virus infections', Virology, vol. 512, pp. 194-200. https://doi.org/10.1016/j.virol.2017.09.021

TY - JOUR

T1 - Antibody-based immunotherapy of aciclovir resistant ocular herpes simplex virus infections

AU - Bauer, Dirk

AU - Keller, Jessica

AU - Alt, Mira

AU - Schubert, Axel

AU - Aufderhorst, Ulrich Wilhelm

AU - Palapys, Vivien

AU - Kasper, Maren

AU - Heilingloh, Christiane Silke

AU - Dittmer, Ulf

AU - Laffer, Björn

AU - Eis-Hübinger, Anna Maria

AU - Verjans, Georges M.

AU - Heiligenhaus, Arnd

AU - Roggendorf, Michael

AU - Krawczyk, Adalbert

PY - 2017/12

Y1 - 2017/12

N2 - 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 24 h prior (pre-exposure prophylaxis) or at 24, 40, and 56 h 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.

AB - 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 24 h prior (pre-exposure prophylaxis) or at 24, 40, and 56 h 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.

KW - ARN

KW - Aciclovir resistance

KW - HSV

KW - Humanized Anti-HSV-antibody

KW - Infection of the eye

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DO - 10.1016/j.virol.2017.09.021

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AN - SCOPUS:85030309099

SN - 0042-6822

VL - 512

SP - 194

EP - 200

JO - Virology

JF - Virology

ER -

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

Abstract

Keywords

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