Protective and therapeutic capacity of human single-chain Fv-Fc fusion proteins against West Nile virus.
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.
Gould
L Hannah
LH
Department of Epidemiology and Public Health, Yale University School of Medicine, New Haven, CT 06520, USA.
Sui
Jianhua
J
Foellmer
Harald
H
Oliphant
Theodore
T
Wang
Tian
T
Ledizet
Michel
M
Murakami
Akikazu
A
Noonan
Kristin
K
Lambeth
Cassandra
C
Kar
Kalipada
K
Anderson
John F
JF
de Silva
Aravinda M
AM
Diamond
Michael S
MS
Koski
Raymond A
RA
Marasco
Wayne A
WA
Fikrig
Erol
E
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*
D000914:Antibodies, Viral; D007141:Immunoglobulin Fc Fragments; D007128:Immunoglobulin Fragments; D011993:Recombinant Fusion Proteins; D014765:Viral Vaccines; C055966:immunoglobulin Fv