Epitopes described in "Development of a humanized monoclonal antibody with therapeutic potential against West Nile virus."

Article Authors:Theodore Oliphant; Michael Engle; Grant E Nybakken; Chris Doane; Syd Johnson; Ling Huang; Sergey Gorlatov; Erin Mehlhop; Anantha Marri; Kyung Min Chung; Gregory D Ebel; Laura D Kramer; Daved H Fremont; Michael S Diamond
Article Title:Development of a humanized monoclonal antibody with therapeutic potential against West Nile virus.
Reference Detail
Reference ID:1173
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.
Affiliations:Department of Molecular Microbiology, Washington University School of Medicine, 660 South Euclid Avenue, Box 8051, St. Louis, Missouri 63110, USA.
Reference Type:Literature
PubMed ID:15852016
Journal:Nat Med
Journal Volume:11
Article Pages:522-30
Journal ISSN:1078-8956
Article Chemical List:Antibodies, Monoclonal;DNA Primers;Viral Envelope Proteins
Article MeSH List:Animals; Antibodies, Monoclonal(immunology); Cloning, Molecular; DNA Primers; Enzyme-Linked Immunosorbent Assay; Epitope Mapping; Humans; Immunotherapy; Mice; Mice, Inbred C57BL; Mutagenesis; Neutralization Tests; Plasmids(genetics); Viral Envelope Proteins(immunology; metabolism); West Nile Fever(immunology; therapy); West Nile virus(immunology); Yeasts
Curation Last Updated:2015-06-05 00:14:43