Protective and herapeutic capacity of human single-chain Fv-Fc fusion proteins against West Nile virus

L. Hannah Gould, Jianhua Sui, Harald Foellmer, Theodore Oliphant, Tian Wang, Michel Ledizet, Akikazu Murakami, Kristin Noonan, Cassandra Lambeth, Kalipada Kar, John F. Anderson, Aravinda M. De Silva, Michael S. Diamond, Raymond A. Koski, Wayne A. Marasco, Erol Fikrig

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100 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)14606-14613
Number of pages8
JournalJournal of Virology
Volume79
Issue number23
DOIs
StatePublished - Dec 2005
Externally publishedYes

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ASJC Scopus subject areas

  • Immunology

Cite this

Gould, L. H., Sui, J., Foellmer, H., Oliphant, T., Wang, T., Ledizet, M., Murakami, A., Noonan, K., Lambeth, C., Kar, K., Anderson, J. F., De Silva, A. M., Diamond, M. S., Koski, R. A., Marasco, W. A., & Fikrig, E. (2005). Protective and herapeutic capacity of human single-chain Fv-Fc fusion proteins against West Nile virus. Journal of Virology, 79(23), 14606-14613. https://doi.org/10.1128/JVI.79.23.14606-14613.2005