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

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.

Keywords: ARN; Aciclovir resistance; HSV; Humanized Anti-HSV-antibody; Infection of the eye.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acyclovir / pharmacology*
  • Animals
  • Antibodies, Monoclonal / therapeutic use*
  • Antibodies, Viral / immunology*
  • Antiviral Agents / pharmacology
  • Drug Resistance, Viral
  • Female
  • Herpesviridae / drug effects*
  • Herpesviridae / immunology
  • Humans
  • Immunotherapy*
  • Mice
  • Mice, Inbred BALB C
  • Retinitis / immunology
  • Retinitis / virology*

Substances

  • Antibodies, Monoclonal
  • Antibodies, Viral
  • Antiviral Agents
  • Acyclovir