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.
authors.affiliation: Department of Molecular Microbiology, Washington University School of Medicine, 660 South Euclid Avenue, Box 8051, St. Louis, Missouri 63110, USA.
authors.forename: Theodore
authors.initials: T
authors.lastname: Oliphant
authors.forename: Michael
authors.initials: M
authors.lastname: Engle
authors.forename: Grant E
authors.initials: GE
authors.lastname: Nybakken
authors.forename: Chris
authors.initials: C
authors.lastname: Doane
authors.forename: Syd
authors.initials: S
authors.lastname: Johnson
authors.forename: Ling
authors.initials: L
authors.lastname: Huang
authors.forename: Sergey
authors.initials: S
authors.lastname: Gorlatov
authors.forename: Erin
authors.initials: E
authors.lastname: Mehlhop
authors.forename: Anantha
authors.initials: A
authors.lastname: Marri
authors.forename: Kyung Min
authors.initials: KM
authors.lastname: Chung
authors.forename: Gregory D
authors.initials: GD
authors.lastname: Ebel
authors.forename: Laura D
authors.initials: LD
authors.lastname: Kramer
authors.forename: Daved H
authors.initials: DH
authors.lastname: Fremont
authors.forename: Michael S
authors.initials: MS
authors.lastname: Diamond
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D003001:Cloning, Molecular; D017931:DNA Primers; D004797:Enzyme-Linked Immunosorbent Assay; D018604:Epitope Mapping; D006801:Humans; D007167:Immunotherapy; D051379:Mice; D008810:Mice, Inbred C57BL; D016296:Mutagenesis; D009500:Neutralization Tests; D010957:Plasmids / Q000235:genetics; D014759:Viral Envelope Proteins / Q000276:immunology* / Q000378:metabolism; D014901:West Nile Fever / Q000276:immunology / Q000628:therapy*; D014902:West Nile virus / Q000276:immunology*; D015003:Yeasts
chemical_list: D000911:Antibodies, Monoclonal; D017931:DNA Primers; D014759:Viral Envelope Proteins