@article{ef7df3a9785d4adaa95303a637e528bc,
title = "Development of a humanized monoclonal antibody with therapeutic potential against West Nile virus",
abstract = "Neutralization of West Nile virus (WNV) in vivo correlates with the development of an antibody response against the viral envelope (E) protein. Using random mutagenesis and yeast surface display, we defined individual contact residues of 14 newly generated monoclonal antibodies against domain III of the WNV E protein. Monoclonal antibodies that strongly neutralized WNV localized to a surface patch on the lateral face of domain III. Convalescent antibodies from individuals who had recovered from WNV infection also detected this epitope. One monoclonal antibody, E16, neutralized 10 different strains in vitro, and showed therapeutic efficacy in mice, even when administered as a single dose 5 d after infection. A humanized version of E16 was generated that retained antigen specificity, avidity and neutralizing activity. In postexposure therapeutic trials in mice, a single dose of humanized E16 protected mice against WNV-induced mortality, and may therefore be a viable treatment option against WNV infection in humans.",
author = "Theodore Oliphant and Michael Engle and Nybakken, {Grant E.} and Chris Doane and Syd Johnson and Ling Huang and Sergey Gorlatov and Erin Mehlhop and Anantha Marri and Chung, {Kyung Min} and Ebel, {Gregory D.} and Kramer, {Laura D.} and Fremont, {Daved H.} and Diamond, {Michael S.}",
note = "Funding Information: The authors thank A. Pekosz, K. Blight, D. Leib, L. Morrison, R. Klein, P. Olivo, and T. Pierson and their laboratories for advice on experiments. The authors thank H. Virgin and D. Goldberg for critical reading of the manuscript, G. Stahl and M. Carroll for complement-deficient mice, and M. Busch and L. Tobler for the human plasma samples. The work was supported by grants from US National Institutes of Health (U01 AI061373 to M.S.D. and U54 AI057160 to the Midwest Regional Center of Excellence for Biodefense and Emerging Infectious Diseases Research), the Pediatric Dengue Vaccine Initiative, the Edward Mallinckrodt Jr. Foundation and a New Scholar Award in Global Infectious Diseases from the Ellison Foundation. C.D. was supported in part by a fellowship funded by an Undergraduate Biological Sciences Education Program grant from the Howard Hughes Medical Institute to Washington University.",
year = "2005",
month = may,
doi = "10.1038/nm1240",
language = "English",
volume = "11",
pages = "522--530",
journal = "Nature medicine",
issn = "1078-8956",
number = "5",
}