Abstract
Despite years of research dedicated to preventing the sexual transmission of herpes simplex virus 2 (HSV-2), there is still no protective vaccine or microbicide against one of the most common sexually transmitted infections in the world. Using a phage display library constructed from a llama immunized with recombinant HSV-2 glycoprotein D, we identified a single-domain antibody VHH, R33, which binds to the viral surface glycoprotein D. Although R33 does not demonstrate any HSV-2 neutralization activity in vitro, when expressed with the cytotoxic domain of exotoxin A, the resulting immunotoxin (R33ExoA) specifically and potently kills HSV-2-infected cells, with a 50% neutralizing dilution (IC50) of 6.7 nM. We propose that R33ExoA could be used clinically to prevent transmission of HSV-2 through killing of virus-producing epithelial cells during virus reactivation. R33 could also potentially be used to deliver other cytotoxic effectors to HSV-2-infected cells.
Copyright © 2015, American Society for Microbiology. All Rights Reserved.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, N.I.H., Intramural
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Research Support, Non-U.S. Gov't
MeSH terms
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ADP Ribose Transferases / genetics
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ADP Ribose Transferases / immunology
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Animals
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Antiviral Agents / pharmacology*
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Bacterial Toxins / genetics
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Bacterial Toxins / immunology
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Camelids, New World
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Chlorocebus aethiops
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Exotoxins / genetics
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Exotoxins / immunology
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Herpesvirus 2, Human / drug effects*
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Immunotoxins / genetics
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Immunotoxins / immunology
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Immunotoxins / pharmacology
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Neutralization Tests
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Pseudomonas aeruginosa Exotoxin A
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Recombinant Fusion Proteins / genetics
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Recombinant Fusion Proteins / immunology
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Recombinant Fusion Proteins / pharmacology
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Single-Domain Antibodies / genetics
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Single-Domain Antibodies / immunology
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Single-Domain Antibodies / pharmacology*
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Toxicity Tests / methods
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Vero Cells / drug effects
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Vero Cells / virology
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Viral Envelope Proteins / metabolism*
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Virulence Factors / genetics
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Virulence Factors / immunology
Substances
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Antiviral Agents
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Bacterial Toxins
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Exotoxins
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Immunotoxins
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Recombinant Fusion Proteins
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Single-Domain Antibodies
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Viral Envelope Proteins
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Virulence Factors
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glycoprotein D-herpes simplex virus type 2
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ADP Ribose Transferases