In Vivo Observations and Electron Microscopy of Treatment of Experimental HSV Keratitis with Anti-HSV Monoclonal Antibodies

摘要

Purpose: To study the antiviral activity of monoclonal antibodies (McAb) in vivo and identify their effects on experimental herpetic keratitis. Methods: Topical use of anti-HSV monoclonal glycoprotein antibodies was carried out on acute herpetic keratitis of rabbits infected by HSV-1 SM_(44). The application of the eye drops in each group was five times per day for 14 days by double-blind method. In vivo observation and electron microscopy were performed during the whole procedure. The anti-HSV McAb's solution was mixed up of five monoclonal antibodies with high neutrilization titers and/or high ADCC activity. Results: Compared with placebo-treated eyes, anti-HSV McAb treatment made statistically significant reduction of herpetic corneal epithelial lesion on rabbits from day 3 to day 14 postinnoculation (P < 0.01). Punctate and short dendritic lesion were the main patterns. The area of involvement was also limited. Electron microscopic analysis showed ultrastructural changes of herpetic corneal infection. The clumping of nuclear chromatin, swollon nuclei, reduction of microfla-ment, rounding of epithelial cells were apparent in placebo-treated eyes. The advanced lesion of the viral infection was karyolysis, karyoklasis and disruption of cells in both scanning and transmission electron micrographes. The management of the McAb-treated eyes showed that the pathological involvements as mentioned above reduced remarkablely. Conclusion: Topical application of anti-HSV monoclonal antibodies produced marked antiviral effects in inhibiting the developement of experimental herpetic keratitis in rabbits and in protecting the susceptible corneal cells. As a new biological product, the anti-HSV monoclonal antibodies may provide a new approach to the treatment of HSV keratits.