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: | , , , , , , , , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
April 8, 2013
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| 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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| 520 | |a 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. | ||
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