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Journal of Virology, December 2005, p. 14606-14613, Vol. 79, No. 23
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.23.14606-14613.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Protective and Therapeutic Capacity of Human Single-Chain Fv-Fc Fusion Proteins against West Nile Virus

L. Hannah Gould,1,2 Jianhua Sui,3 Harald Foellmer,2 Theodore Oliphant,4 Tian Wang,2 Michel Ledizet,6 Akikazu Murakami,3 Kristin Noonan,3 Cassandra Lambeth,7 Kalipada Kar,6 John F. Anderson,8 Aravinda M. de Silva,7 Michael S. Diamond,4,5 Raymond A. Koski,6 Wayne A. Marasco,3 and Erol Fikrig1,2*

Department of Epidemiology and Public Health,1 Section of Rheumatology, Department of Internal Medicine, Yale School of Medicine, New Haven, Connecticut,2 Department of Cancer Immunology and AIDS, Dana Farber Cancer Institute, Boston, Massachusetts,3 Department of Molecular Microbiology,4 Medicine, Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri,5 L Diagnostics, New Haven, Connecticut;,6 Department of Microbiology and Immunology, University of North Carolina, Chapel Hill, North Carolina,7 Connecticut Agricultural Experiment Station, New Haven, Connecticut8

Received 22 March 2005/ Accepted 29 August 2005

West Nile virus has spread rapidly across the United States, and there is currently no approved human vaccine or therapy to prevent or treat disease. Passive immunization with antibodies against the envelope protein represents a promising means to provide short-term prophylaxis and treatment for West Nile virus infection. In this study, we identified a panel of 11 unique human single-chain variable region antibody fragments (scFvs) that bind the envelope protein of West Nile virus. Selected scFvs were converted to Fc fusion proteins (scFv-Fcs) and were tested in mice for their ability to prevent lethal West Nile virus infection. Five of these scFv-Fcs, 11, 15, 71, 85, and 95, protected 100% of mice from death when given prior to infection with virus. Two of them, 11 and 15, protected 80% of mice when given at days 1 and 4 after infection. In addition, four of the scFv-Fcs cross-neutralized dengue virus, serotype 2. Binding assays using yeast surface display demonstrated that all of our scFvs bind to sites within domains I and II of West Nile virus envelope protein. These recombinant human scFvs are potential candidates for immunoprophylaxis and therapy of flavivirus infections.

* Corresponding author. Mailing address: Section of Rheumatology, Department of Internal Medicine, Yale University School of Medicine, The Anlyan Center for Medical Research, Room S525A, 300 Cedar St., New Haven, CT 06520-8031. Phone: (203) 785-2453. Fax: (203) 785-7053. E-mail: erol.fikrig{at}yale.edu.

Journal of Virology, December 2005, p. 14606-14613, Vol. 79, No. 23
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.23.14606-14613.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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