RECOMBINANT HUMAN FAB TO GLYCOPROTEIN-D NEUTRALIZES INFECTIVITY AND PREVENTS CELL-TO-CELL TRANSMISSION OF HERPES-SIMPLEX VIRUS-1 AND VIRUS-2 IN-VITRO

Herpes simplex viruses 1 and 2 (HSV-1 and -2) are associated with a nu mber of conditions of varying severity, which are only partially respo nsive to current therapies. Human antibodies to the viruses offer a po tential alternative. We describe here the generation of panels of huma n monoclonal Fab fragments to HSV-1 and -2 by panning a phage display combinatorial antibody library against whole lysates from the two viru ses. Each lysate selected a largely distinct set of Fabs, although all of the Fabs were cross-reactive with both viruses. In a plaque-reduct ion assay, one Fab neutralized HSV-1 at 0.25 mug/ml (50% reduction) an d HSV-2 at 0.05 mug/ml. This Fab also inhibited plaque formation when applied to virus-infected monolayers, completely abolishing HSV-2 plaq ue development at 25 mug/ml 72 hr postinfection, indicating the abilit y of the Fab to prevent cell-to-cell spread of virus. The Fab was show n to recognize viral glycoprotein D and to neutralize virus primarily by a postattachment mechanism. Recombinant Fabs may be useful for topi cal administration, although whole antibody will probably be required for systemic use.