Antibodies targeting linear determinants of the envelope protein protect mice against West Nile virus.
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.
Ledizet
Michel
M
L2 Diagnostics, Department of Internal Medicine, Yale School of Medicine, 300 George Street, New Haven, CT 06525, USA. mledizet@L2Dx.com
Kar
Kalipada
K
Foellmer
Harald G
HG
Bonafé
Nathalie
N
Anthony
Karen G
KG
Gould
L Hannah
LH
Bushmich
Sandra L
SL
Fikrig
Erol
E
Koski
Raymond A
RA
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*
D000914:Antibodies, Viral; D000939:Epitopes; D007136:Immunoglobulins; D010446:Peptide Fragments; D014759:Viral Envelope Proteins; C065696:glycoprotein E, Flavivirus