Antiviral activity of a single-domain antibody immunotoxin binding to glycoprotein D of herpes simplex virus 2

Eileen M. Geoghegan, Hong Zhang, Prashant J. Desai, Arya Biragyn, Richard B. Markham

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)527-535
Number of pages9
JournalAntimicrobial agents and chemotherapy
Volume59
Issue number1
DOIs
StatePublished - Jan 1 2015

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)
  • Infectious Diseases

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