TY - JOUR
T1 - Antiviral activity of a single-domain antibody immunotoxin binding to glycoprotein D of herpes simplex virus 2
AU - Geoghegan, Eileen M.
AU - Zhang, Hong
AU - Desai, Prashant J.
AU - Biragyn, Arya
AU - Markham, Richard B.
N1 - Publisher Copyright:
© 2015 American Society for Microbiology. All Rights Reserved.
PY - 2015/1/1
Y1 - 2015/1/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84920137077&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84920137077&partnerID=8YFLogxK
U2 - 10.1128/AAC.03818-14
DO - 10.1128/AAC.03818-14
M3 - Article
C2 - 25385102
AN - SCOPUS:84920137077
SN - 0066-4804
VL - 59
SP - 527
EP - 535
JO - Antimicrobial Agents and Chemotherapy
JF - Antimicrobial Agents and Chemotherapy
IS - 1
ER -