title: Antibodies targeting linear determinants of the envelope protein protect mice against West Nile virus.
abstract: The flavivirus envelope (E) protein mediates cellular attachment and fusion with host cell membranes and is recognized by virus-neutralizing antibodies. We raised antibodies against a broad range of epitopes by immunizing a horse with recombinant West Nile virus (WNV) E protein. To define epitopes recognized by protective antibodies, we selected, by affinity chromatography, immunoglobulins against immobilized linear peptides derived from parts of the E protein. Immunoglobulins binding 9 different peptides from domains I, II, and III of the E protein neutralized WNV in vitro. This indicates that multiple protective epitopes can be found in the E protein. Immunoglobulins recognizing 3 peptides derived from domains I and II of E protein protected mice against a lethal challenge with WNV. These immunoglobulins recognized the E proteins of related flaviviruses, demonstrating that antibodies targeting specific E protein epitopes could be developed for prevention and treatment of multiple flavivirus infections.
authors.affiliation: L2 Diagnostics, Department of Internal Medicine, Yale School of Medicine, 300 George Street, New Haven, CT 06525, USA. mledizet@L2Dx.com
authors.forename: Michel
authors.initials: M
authors.lastname: Ledizet
authors.forename: Kalipada
authors.initials: K
authors.lastname: Kar
authors.forename: Harald G
authors.initials: HG
authors.lastname: Foellmer
authors.forename: Nathalie
authors.initials: N
authors.lastname: Bonafé
authors.forename: Karen G
authors.initials: KG
authors.lastname: Anthony
authors.forename: L Hannah
authors.initials: LH
authors.lastname: Gould
authors.forename: Sandra L
authors.initials: SL
authors.lastname: Bushmich
authors.forename: Erol
authors.initials: E
authors.lastname: Fikrig
authors.forename: Raymond A
authors.initials: RA
authors.lastname: Koski
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology* / Q000494:pharmacology; D000915:Antibody Affinity / Q000276:immunology; D002522:Chlorocebus aethiops; D004330:Drosophila; D000939:Epitopes / Q000276:immunology; D005260:Female; D005455:Fluorescent Antibody Technique / Q000379:methods; D006736:Horses; D007116:Immunization, Passive / Q000379:methods*; D007136:Immunoglobulins / Q000276:immunology*; D051379:Mice; D008809:Mice, Inbred C3H; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000276:immunology; D014709:Vero Cells; D014759:Viral Envelope Proteins / Q000276:immunology*; D014901:West Nile Fever / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D014902:West Nile virus / Q000276:immunology*
chemical_list: D000914:Antibodies, Viral; D000939:Epitopes; D007136:Immunoglobulins; D010446:Peptide Fragments; D014759:Viral Envelope Proteins; C065696:glycoprotein E, Flavivirus