Characterization of neutralizing antibodies to West Nile virus

• Published in: Virology (New York, N.Y.) Vol. 336; no. 1; pp. 70 - 82
• Main Authors: Sánchez, Melissa D., Pierson, Theodore C., McAllister, Douglas, Hanna, Sheri L., Puffer, Bridget A., Valentine, Laura E., Murtadha, Mariam M., Hoxie, James A., Doms, Robert W.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 25.05.2005
• Subjects: Animals; Antibodies, Monoclonal - immunology; Antibodies, Viral - immunology; Antigens, Viral - immunology; Cross Reactions; disease control; Encephalitis Virus, Japanese - immunology; Encephalitis Virus, St. Louis - immunology; Encephalitis Viruses, Tick-Borne - immunology; Enzyme-Linked Immunosorbent Assay; Epitope Mapping; epitopes; Epitopes - immunology; Flavivirus; glycoproteins; Glycoproteins - immunology; Mice; Monoclonal antibodies; Neutralization; Neutralization Tests; Protein Structure, Tertiary; viral antibodies; viral antigens; viral envelope proteins; viral proteins; West Nile virus; West Nile virus - immunology; Yellow fever virus - immunology; Monoclonal antibodies; Flavivirus; West Nile virus; Neutralization
• ISSN: 0042-6822; 1096-0341
• DOI: 10.1016/j.virol.2005.02.020

We produced nine monoclonal antibodies (MAbs) directed against the West Nile virus E glycoprotein using three different immunization strategies: inactivated virus, naked DNA, and recombinant protein. Most of the MAbs bound to conformation dependent epitopes in domain III of the E protein. Four of the MAbs neutralized WNV infection and bound to the same region of domain III with high affinity. The neutralizing MAbs were obtained from mice immunized with inactivated virus alone or in combination with a DNA plasmid. In contrast, MAbs obtained by immunization with a soluble version of the E glycoprotein did not exhibit neutralizing activity. These non-neutralizing antibodies were cross-reactive with several other flaviviruses, including Saint Louis encephalitis, Japanese encephalitis, Yellow Fever and Powassan viruses. Interestingly, some non-neutralizing MAbs bound with high affinity to domains I or III, indicating that both affinity and the precise epitope recognized by an antibody are important determinants of WNV neutralization.