A monoclonal antibody targeting the HSV-1/2 glycoprotein B inhibits the development herpes simplex virus type 1 retinitis in mice

Abstract

Purpose : The increasing incidence of antiviral drug-resistant strains in patients with ocular HSV-1 infection is a major health problem that may lead to blindness. The present study was undertaken to investigate whether the treatment of mice with a murine or humanized monoclonal antibody targeting HSV-gB (mAb 2c / hu2c) may be able to prevent the development of herpes simplex virus 1 (HSV-1) retinitis in mice.

Methods : HSV-retinitis was induced on day 0 by the injection of HSV-1 KOS strain (or an acyclovir resistant HSV-1 isolate) into the anterior chamber (AC) of the right eyes of BALB/c mice. Systemic treatment was performed by intravenous administration of mAb 2c / hu2c at 24 h prior to infection (pre-exposure prophylaxis), or 24, 40, and 56 hours after inoculation (post-exposure immunotherapy). The clinical course of acute retinal necrosis (ARN), virus-neutralizing antibody titers, and viral content in the eyes were determined.

Results : Systemic antibody treatment markedly reduced the viral loads at the site of primary infection, and protected the contralateral eyes from developing ARN. The administration of the antiviral antibody prior or post infection was equally effective. A similar observation was found, when an acyclovir resistant virus was used for the infection. Topical treatment did not improve the severity of disease. After systemic treatment with mAb hu2c, the human antibody targeting HSV-1 could be detected at the contralateral retina, indicating that systemically applied mAb is able to reach this site of infection.

Conclusions : Our data show that the mAb 2c or hu2c are an effective treatment option for intraocular HSV-infections, and for the prevention of contralateral acute retinal necrosis and the secondary blindness. These results warrant the future use of this antibody as a novel approach for the treatment of ACV resistant HSV-infections in humans.

This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.