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.

journal_name

J Virol

journal_title

Journal of virology

authors

Gould LH,Sui J,Foellmer H,Oliphant T,Wang T,Ledizet M,Murakami A,Noonan K,Lambeth C,Kar K,Anderson JF,de Silva AM,Diamond MS,Koski RA,Marasco WA,Fikrig E

doi

10.1128/JVI.79.23.14606-14613.2005

subject

Has Abstract

pub_date

2005-12-01 00:00:00

pages

14606-13

issue

23

eissn

0022-538X

issn

1098-5514

pii

79/23/14606

journal_volume

79

pub_type

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