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

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
Proceedings of the National Academy of Sciences of the United States of America
Vol. 110, No. 17 (April 23, 2013), pp. 6760-6765
Stable URL: http://www.jstor.org/stable/42590512
Page Count: 6
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Overcoming drug-resistant herpes simplex virus (HSV) infection by a humanized antibody
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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 drugresistant HSV infections.

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