title: Overcoming drug-resistant herpes simplex virus (HSV) infection by a humanized antibody.
abstract: Despite the availability of antiviral chemotherapy, herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) infections remain a severe global health problem. Of particular concern is the growing incidence of drug resistance in immunocompromised patients, which stresses the urgency to develop new effective treatment alternatives. We have developed a humanized monoclonal antibody (mAb hu2c) that completely abrogates viral cell-to-cell spread, a key mechanism by which HSV-1/2 escapes humoral immune surveillance. Moreover, mAb hu2c neutralized HSV fully independent of complement and/or immune effector cell recruitment in a highly efficient manner. Prophylactic and therapeutic administration of mAb hu2c completely prevented infection-related mortality of severely immunodeficient mice being challenged with a lethal dose of HSV-1. The high neutralization capacity of mAb hu2c was fully maintained toward clinical HSV isolates being multiresistant to standard antiviral drugs, and infection was fully resolved in 7/8 nonobese diabetic/SCID mice being infected with a multidrug resistant HSV-1 patient isolate. Immunohistochemical studies revealed no significant cross-reactivity of the antibody toward human tissues. These features warrant further clinical development of mAb hu2c as an immunotherapeutic compound for the management of severe and particularly drug-resistant HSV infections.
authors.affiliation: Institute of Virology, University Hospital Essen, University of Duisburg-Essen, 45122 Essen, Germany.
authors.forename: Adalbert
authors.initials: A
authors.lastname: Krawczyk
authors.forename: Michaela A E
authors.initials: MA
authors.lastname: Arndt
authors.forename: Ludger
authors.initials: L
authors.lastname: Grosse-Hovest
authors.forename: Wilko
authors.initials: W
authors.lastname: Weichert
authors.forename: Bernd
authors.initials: B
authors.lastname: Giebel
authors.forename: Ulf
authors.initials: U
authors.lastname: Dittmer
authors.forename: Hartmut
authors.initials: H
authors.lastname: Hengel
authors.forename: Dirk
authors.initials: D
authors.lastname: Jäger
authors.forename: Karl E
authors.initials: KE
authors.lastname: Schneweis
authors.forename: Anna M
authors.initials: AM
authors.lastname: Eis-Hübinger
authors.forename: Michael
authors.initials: M
authors.lastname: Roggendorf
authors.forename: Jürgen
authors.initials: J
authors.lastname: Krauss
mesh_terms: D000212:Acyclovir; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000627:therapeutic use*; D000914:Antibodies, Viral / Q000276:immunology / Q000627:therapeutic use*; D002522:Chlorocebus aethiops; D024882:Drug Resistance, Viral; D006561:Herpes Simplex / Q000188:drug therapy* / Q000276:immunology; D007150:Immunohistochemistry; D051379:Mice; D016513:Mice, SCID; D008856:Microscopy, Fluorescence; D009500:Neutralization Tests; D018139:Simplexvirus / Q000235:genetics / Q000276:immunology*; D014709:Vero Cells
chemical_list: D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral; D000212:Acyclovir