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

14 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",

note = "Publisher Copyright: {\textcopyright} 2017 The Authors",

year = "2017",

month = dec,

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

language = "English",

volume = "512",

pages = "194--200",

journal = "Virology",

issn = "0042-6822",

publisher = "Academic Press Inc.",

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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

UR - https://www.scopus.com/pages/publications/85030309099

U2 - 10.1016/j.virol.2017.09.021

DO - 10.1016/j.virol.2017.09.021

M3 - Article

C2 - 28985573

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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