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Journal of Virology, March 2004, p. 2562-2571, Vol. 78, No. 5
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.5.2562-2571.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Immunization Strategies To Block the Herpes Simplex Virus Type 1 Immunoglobulin G Fc Receptor

Xiaoqing Lin,{dagger} John M. Lubinski, and Harvey M. Friedman*

Department of Medicine, Division of Infectious Diseases, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104

Received 23 September 2003/ Accepted 29 October 2003

Herpes simplex virus type 1 (HSV-1) glycoprotein gE functions as an immunoglobulin G (IgG) Fc receptor (Fc{gamma}R) that promotes immune evasion. When an IgG antibody binds by the F(ab')2 domain to an HSV antigen, the Fc domain of some of the same antibody molecules binds to the Fc{gamma}R, which blocks Fc-mediated functions. gE is a type 1 membrane glycoprotein with a large ectodomain that is expressed on the virion envelope and infected-cell surface. Our goal was to determine if immunizing with gE protein fragments could produce antibodies that bind by the F(ab')2 domain to gE and block the Fc{gamma}R, as measured by competitively inhibiting nonimmune human IgG binding to the Fc{gamma}R. Three gE peptides were constructed in baculovirus spanning almost the entire ectodomain and used to immunize mice and rabbits. Two fragments were highly effective at producing antibodies that bind by the F(ab')2 domain and block the Fc{gamma}R. The most potent of these two antibodies was far more effective at blocking the Fc{gamma}R than antibodies that are only capable of binding by the Fc domains to the Fc{gamma}R, including anti-gC, anti-gD, and nonimmune IgG. These results suggest that immunizing with gE fragments has potential for preventing immune evasion by blocking activities mediated by the HSV-1 Fc{gamma}R.

* Corresponding author. Mailing address: 502 Johnson Pavilion, University of Pennsylvania, Philadelphia, PA 19104-6073. Phone: (215) 662-3557. Fax: (215) 349-5111. E-mail: hfriedma{at}mail.med.upenn.edu.

{dagger} Present address: Department of Pathology, University of Maryland Medical System, Baltimore, MD 21201-1595.

Journal of Virology, March 2004, p. 2562-2571, Vol. 78, No. 5
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.5.2562-2571.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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