Recombinant human Fab to glycoprotein D neutralizes infectivity and prevents cell-to-cell transmission of herpes simplex viruses 1 and 2 in vitro

Roberto Burioni, R. Anthony Williamson, Pietro Paolo Sanna, Floyd E. Bloom, Dennis R. Burton

Research output: Contribution to journalArticle

Abstract

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 μg/ml (50% reduction) and HSV-2 at 0.05 μg/ml. This Fab also inhibited plaque formation when applied to virus-infected monolayers, completely abolishing HSV-2 plaque development at 25 μg/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.

Original languageEnglish
Pages (from-to)355-359
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume91
Issue number1
DOIs
Publication statusPublished - Jan 4 1994

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Keywords

  • human antibody repertoires
  • immune prophylaxis
  • phage surface expression
  • virus neutralization

ASJC Scopus subject areas

  • Genetics
  • General

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