Prevention of herpes simplex virus induced stromal keratitis by a glycoprotein B-specific monoclonal antibody

PLoS One. 2015 Jan 14;10(1):e0116800. doi: 10.1371/journal.pone.0116800. eCollection 2015.

Abstract

The increasing incidence of acyclovir (ACV) and multidrug-resistant strains in patients with corneal HSV-1 infections leading to Herpetic Stromal Keratitis (HSK) is a major health problem in industrialized countries and often results in blindness. To overcome this obstacle, we have previously developed an HSV-gB-specific monoclonal antibody (mAb 2c) that proved to be highly protective in immunodeficient NOD/SCID-mice towards genital infections. In the present study, we examined the effectivity of mAb 2c in preventing the immunopathological disease HSK in the HSK BALB/c mouse model. Therefore, mice were inoculated with HSV-1 strain KOS on the scarified cornea to induce HSK and subsequently either systemically or topically treated with mAb 2c. Systemic treatment was performed by intravenous administration of mAb 2c 24 h prior to infection (pre-exposure prophylaxis) or 24, 40, and 56 hours after infection (post-exposure immunotherapy). Topical treatment was performed by periodical inoculations (5 times per day) of antibody-containing eye drops as control, starting at 24 h post infection. Systemic antibody treatment markedly reduced viral loads at the site of infection and completely protected mice from developing HSK. The administration of the antiviral antibody prior or post infection was equally effective. Topical treatment had no improving effect on the severity of HSK. In conclusion, our data demonstrate that mAb 2c proved to be an excellent drug for the treatment of corneal HSV-infections and for prevention of HSK and blindness. Moreover, the humanized counterpart (mAb hu2c) was equally effective in protecting mice from HSV-induced HSK when compared to the parental mouse antibody. These results warrant the future development of this antibody as a novel approach for the treatment of corneal HSV-infections in humans.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acyclovir / immunology
  • Animals
  • Antibodies, Monoclonal / immunology*
  • Antiviral Agents / immunology
  • Chlorocebus aethiops
  • Corneal Stroma / immunology
  • Corneal Stroma / virology
  • Female
  • Glycoproteins / immunology*
  • Herpes Simplex / complications
  • Herpes Simplex / virology
  • Immunoglobulins / immunology
  • Keratitis, Herpetic / etiology
  • Keratitis, Herpetic / immunology*
  • Keratitis, Herpetic / prevention & control*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Simplexvirus / immunology*
  • Vero Cells

Substances

  • Antibodies, Monoclonal
  • Antiviral Agents
  • Glycoproteins
  • Immunoglobulins
  • immunoglobulin B
  • Acyclovir

Grant support

This study was funded by the “Ernst und Berta Grimmke-Stiftung” Foundation (grant number 1/13, awarded to AK). Anna Buch and Beate Sodeik are supported by the Niedersachsen-Research Network on Neuroinfectiology (N-RENNT) of the Ministry of Science and Culture of Lower Saxony, Germany. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.