title: Protective and therapeutic capacity of human single-chain Fv-Fc fusion proteins against West Nile virus.
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.
authors.affiliation: Department of Epidemiology and Public Health, Yale University School of Medicine, New Haven, CT 06520, USA.
authors.forename: L Hannah
authors.initials: LH
authors.lastname: Gould
authors.forename: Jianhua
authors.initials: J
authors.lastname: Sui
authors.forename: Harald
authors.initials: H
authors.lastname: Foellmer
authors.forename: Theodore
authors.initials: T
authors.lastname: Oliphant
authors.forename: Tian
authors.initials: T
authors.lastname: Wang
authors.forename: Michel
authors.initials: M
authors.lastname: Ledizet
authors.forename: Akikazu
authors.initials: A
authors.lastname: Murakami
authors.forename: Kristin
authors.initials: K
authors.lastname: Noonan
authors.forename: Cassandra
authors.initials: C
authors.lastname: Lambeth
authors.forename: Kalipada
authors.initials: K
authors.lastname: Kar
authors.forename: John F
authors.initials: JF
authors.lastname: Anderson
authors.forename: Aravinda M
authors.initials: AM
authors.lastname: de Silva
authors.forename: Michael S
authors.initials: MS
authors.lastname: Diamond
authors.forename: Raymond A
authors.initials: RA
authors.lastname: Koski
authors.forename: Wayne A
authors.initials: WA
authors.lastname: Marasco
authors.forename: Erol
authors.initials: E
authors.lastname: Fikrig
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology*; D000918:Antibody Specificity / Q000276:immunology; D006801:Humans; D007141:Immunoglobulin Fc Fragments / Q000627:therapeutic use*; D007128:Immunoglobulin Fragments / Q000737:chemistry / Q000627:therapeutic use*; D051379:Mice; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology / Q000627:therapeutic use; D014765:Viral Vaccines / Q000276:immunology*; D014901:West Nile Fever / Q000517:prevention & control*; D014902:West Nile virus / Q000276:immunology* / Q000472:pathogenicity*
chemical_list: D000914:Antibodies, Viral; D007141:Immunoglobulin Fc Fragments; D007128:Immunoglobulin Fragments; D011993:Recombinant Fusion Proteins; D014765:Viral Vaccines; C055966:immunoglobulin Fv