Recombinant human Fab to glycoprotein D neutralizes infectivity and prevents cell-to-cell transmission of herpes simplex viruses 1 and 2 in vitro.
Herpes simplex viruses 1 and 2 (HSV-1 and -2) are associated with a number of conditions of varying severity, which are only partially responsive to current therapies. Human antibodies to the viruses offer a potential alternative. We describe here the generation of panels of human monoclonal Fab fragments to HSV-1 and -2 by panning a phage display combinatorial antibody library against whole lysates from the two viruses. Each lysate selected a largely distinct set of Fabs, although all of the Fabs were cross-reactive with both viruses. In a plaque-reduction assay, one Fab neutralized HSV-1 at 0.25 microgram/ml (50% reduction) and HSV-2 at 0.05 microgram/ml. This Fab also inhibited plaque formation when applied to virus-infected monolayers, completely abolishing HSV-2 plaque development at 25 micrograms/ml 72 hr postinfection, indicating the ability of the Fab to prevent cell-to-cell spread of virus. The Fab was shown to recognize viral glycoprotein D and to neutralize virus primarily by a postattachment mechanism. Recombinant Fabs may be useful for topical administration, although whole antibody will probably be required for systemic use.
Burioni
R
R
Department of Immunology, Scripps Research Institute, La Jolla, CA 92037.
Williamson
R A
RA
Sanna
P P
PP
Bloom
F E
FE
Burton
D R
DR
D000595:Amino Acid Sequence; D000818:Animals; D000914:Antibodies, Viral / Q000737:chemistry* / Q000276:immunology; D002460:Cell Line; D002522:Chlorocebus aethiops; D018259:Herpesvirus 1, Human / Q000276:immunology*; D018258:Herpesvirus 2, Human / Q000276:immunology*; D006801:Humans; D007140:Immunoglobulin Fab Fragments; D008969:Molecular Sequence Data; D009500:Neutralization Tests; D011994:Recombinant Proteins; D014759:Viral Envelope Proteins / Q000276:immunology*
D000914:Antibodies, Viral; D007140:Immunoglobulin Fab Fragments; D011994:Recombinant Proteins; D014759:Viral Envelope Proteins; C039447:glycoprotein D, Human herpesvirus 1; C040570:glycoprotein D-herpes simplex virus type 2