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

89 Citations (Scopus)

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

Fingerprint

Human Herpesvirus 2
Human Herpesvirus 1
Glycoproteins
Viruses
Antibodies
Topical Administration
Immunoglobulin Fab Fragments
Bacteriophages
In Vitro Techniques

Keywords

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

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Recombinant human Fab to glycoprotein D neutralizes infectivity and prevents cell-to-cell transmission of herpes simplex viruses 1 and 2 in vitro. / Burioni, Roberto; Williamson, R. Anthony; Sanna, Pietro Paolo; Bloom, Floyd E.; Burton, Dennis R.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 91, No. 1, 04.01.1994, p. 355-359.

Research output: Contribution to journalArticle

@article{ca0e8ccf95654bfe89a4818405fa16da,
title = "Recombinant human Fab to glycoprotein D neutralizes infectivity and prevents cell-to-cell transmission of herpes simplex viruses 1 and 2 in vitro",
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.",
keywords = "human antibody repertoires, immune prophylaxis, phage surface expression, virus neutralization",
author = "Roberto Burioni and Williamson, {R. Anthony} and Sanna, {Pietro Paolo} and Bloom, {Floyd E.} and Burton, {Dennis R.}",
year = "1994",
month = "1",
day = "4",
doi = "10.1073/pnas.91.1.355",
language = "English",
volume = "91",
pages = "355--359",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
number = "1",

}

TY - JOUR

T1 - Recombinant human Fab to glycoprotein D neutralizes infectivity and prevents cell-to-cell transmission of herpes simplex viruses 1 and 2 in vitro

AU - Burioni, Roberto

AU - Williamson, R. Anthony

AU - Sanna, Pietro Paolo

AU - Bloom, Floyd E.

AU - Burton, Dennis R.

PY - 1994/1/4

Y1 - 1994/1/4

N2 - 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.

AB - 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.

KW - human antibody repertoires

KW - immune prophylaxis

KW - phage surface expression

KW - virus neutralization

UR - http://www.scopus.com/inward/record.url?scp=0028082433&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0028082433&partnerID=8YFLogxK

U2 - 10.1073/pnas.91.1.355

DO - 10.1073/pnas.91.1.355

M3 - Article

VL - 91

SP - 355

EP - 359

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

SN - 0027-8424

IS - 1

ER -