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Journal of Virology, December 2003, p. 12639-12645, Vol. 77, No. 23
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.23.12639-12645.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Blocking Immune Evasion as a Novel Approach for Prevention and Treatment of Herpes Simplex Virus Infection

Kara A. Judson,^1, John M. Lubinski,¹ Ming Jiang,¹ Yueh Chang,¹ Roselyn J. Eisenberg,² Gary H. Cohen,³ and Harvey M. Friedman^1*

Infectious Disease Division, Department of Medicine, School of Medicine,¹ Department of Pathobiology, School of Veterinary Medicine,² Department of Microbiology, School of Dental Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104-6073³

Received 1 July 2003/ Accepted 27 August 2003

Many microorganisms encode immune evasion molecules to escape host defenses. Herpes simplex virus type 1 glycoprotein gC is an immunoevasin that inhibits complement activation by binding complement C3b. gC is expressed on the virus envelope and infected cell surface, which makes gC potentially accessible to blocking antibodies. Mice passively immunized with gC monoclonal antibodies prior to infection were protected against herpes simplex virus challenge only if the gC antibodies blocked C3b binding. Mice treated 1 or 2 days postinfection with gC monoclonal antibodies that block C3b binding had less severe disease than control mice treated with nonimmune immunoglobulin G (IgG). Mice immunized with gC protein produced antibodies that blocked C3b binding to gC. Immunized mice were significantly protected against challenge by wild-type virus, but not against a gC mutant virus lacking the C3b binding domain, suggesting that protection was mediated by antibodies that target the gC immune evasion domain. IgG and complement from subjects immunized with an experimental herpes simplex virus glycoprotein gD vaccine neutralized far more mutant virus defective in immune evasion than wild-type virus, supporting the importance of immune evasion molecules in reducing vaccine potency. These results suggest that it is possible to block immune evasion domains on herpes simplex virus and that this approach has therapeutic potential and may enhance vaccine efficacy.

Present address: Johns Hopkins Hospital, Baltimore, MD 21287.

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