Antiviral activity of a single-domain antibody immunotoxin binding to glycoprotein D of herpes simplex virus 2.
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.
The W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, USA.
Eileen M
EM
Geoghegan
The W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, USA.
Hong
H
Zhang
Viral Oncology Program, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Johns Hopkins University, Baltimore, Maryland, USA.
Prashant J
PJ
Desai
Immunoregulation Section, Laboratory of Molecular Biology and Immunology, National Institute on Aging, Baltimore, Maryland, USA.
Arya
A
Biragyn
The W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, USA rmarkha1@jhu.edu.
Richard B
RB
Markham
D036002:ADP Ribose Transferases / Q000235:genetics / Q000276:immunology; D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D001427:Bacterial Toxins / Q000235:genetics / Q000276:immunology; D002161:Camelids, New World; D002522:Chlorocebus aethiops; D005098:Exotoxins / Q000235:genetics / Q000276:immunology; D018258:Herpesvirus 2, Human / Q000187:drug effects*; D000922:Immunotoxins / Q000235:genetics / Q000276:immunology / Q000494:pharmacology; D009500:Neutralization Tests; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology / Q000494:pharmacology; D061905:Single-Domain Antibodies / Q000235:genetics / Q000276:immunology / Q000494:pharmacology*; D018675:Toxicity Tests / Q000379:methods; D014709:Vero Cells / Q000187:drug effects / Q000821:virology; D014759:Viral Envelope Proteins / Q000378:metabolism*; D037521:Virulence Factors / Q000235:genetics / Q000276:immunology; D000097668:Pseudomonas aeruginosa Exotoxin A
D036002:ADP Ribose Transferases; D000998:Antiviral Agents; D001427:Bacterial Toxins; D005098:Exotoxins; D000922:Immunotoxins; D011993:Recombinant Fusion Proteins; D061905:Single-Domain Antibodies; D014759:Viral Envelope Proteins; D037521:Virulence Factors; D000097668:Pseudomonas aeruginosa Exotoxin A; C040570:glycoprotein D-herpes simplex virus type 2