Purpose. Herpes simplex virus (HSV) can cause corneal infections in humans
and lead to permanent scarring, loss of vision, and blindness. Current trea
tment of epithelial HSV keratitis consists of using antiviral DNA analogs.
In this study, we used in vitro and in vivo models to evaluate the efficacy
of six polyclonal antibodies to HSV recombinant surface glycoprotein D in
treating ocular epithelial HSV. Methods. Confluent cultures of African Gree
n monkey kidney fibroblasts (Vero cells) and normal 3- to 5-lb female New Z
ealand White rabbits were infected with HSV type 1, strain RE. In vitro vir
ucidal and antiviral assays were performed, and the best of the compounds w
as chosen for the in vivo stage. Animals were carefully monitored until day
5 after HSV-1 inoculation, then arbitrarily divided into groups receiving,
for 14 days, Varying doses of: polyclonal antibodies four times a day, pol
yclonal antibodies three times a day, trifluorothymidine (current treatment
of choice and the positive control) nine times a day, or 0.9% physiologic
saline nine times a day. The animals were followed up in a masked fashion a
nd carefully monitored for severity and resolution of the HSV infection by
biomicroscopy (slit lamp) examination and viral cultures using standardized
plaque assays. Results. All six of the compounds tested were effective in
vitro, but one compound in particular, SP-510-50, was superior. It was used
for the in vivo testing and showed antiviral efficacy in a dose-dependent
manner, and at dosing four times a day, it was of comparable efficacy to tr
ifluorothymidine (nine times a day). Conclusions. We conclude that polyclon
al antibodies to glycoprotein D appear to be effective antiviral agents in
vitro and in vivo in a rabbit model of HSV-1 keratitis and show promise as
a new antiviral treatment for ophthalmic use.