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Overcoming drug-resistant herpes simplex virus (HSV) infection by a humanized antibody

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 effe...

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Main Authors: Krawczyk, Adalbert (Author) , Arndt, Michaela (Author) , Große-Hovest, Ludger (Author) , Weichert, Wilko (Author) , Giebel, Bernd (Author) , Dittmer, Ulf (Author) , Hengel, Hartmut (Author) , Jäger, Dirk (Author) , Schneweis, Karl E. (Author) , Eis-Hübinger, Anna Maria (Author) , Roggendorf, Michael (Author) , Krauß, Jürgen (Author)
Format: Article (Journal)
Language:English
Published: April 8, 2013
In: Proceedings of the National Academy of Sciences of the United States of America
Year: 2013, Volume: 110, Issue: 17, Pages: 6760-6765
ISSN:1091-6490
DOI:10.1073/pnas.1220019110
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1073/pnas.1220019110
Verlag, lizenzpflichtig, Volltext: https://www.pnas.org/content/110/17/6760
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Author Notes:Adalbert Krawczyk, Michaela A.E. Arndt, Ludger Grosse-Hovest, Wilko Weichert, Bernd Giebel, Ulf Dittmer, Hartmut Hengel, Dirk Jäger, Karl E. Schneweis, Anna M. Eis-Hübinger, Michael Roggendorf, and Jürgen Krauss
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Summary: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.
Item Description:Gesehen am 27.10.2021
Physical Description:Online Resource
ISSN:1091-6490
DOI:10.1073/pnas.1220019110

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