Details

Autor(en) / Beteiligte

• Goo, Leslie
• Debbink, Kari
• Kose, Nurgun
• Sapparapu, Gopal
• Doyle, Michael P
• Wessel, Alex W
• Richner, Justin M
• Burgomaster, Katherine E
• Larman, Bridget C
• Dowd, Kimberly A
• Diamond, Michael S
• Crowe, Jr, James E
• Pierson, Theodore C

Titel

A protective human monoclonal antibody targeting the West Nile virus E protein preferentially recognizes mature virions

Ist Teil von

• Nature microbiology, 2019-01, Vol.4 (1), p.71-77

Ort / Verlag

England

Erscheinungsjahr

2019

Quelle

MEDLINE

Beschreibungen/Notizen

• West Nile virus (WNV), a member of the Flavivirus genus, is a leading cause of viral encephalitis in the United States . The development of neutralizing antibodies against the flavivirus envelope (E) protein is critical for immunity and vaccine protection . Previously identified candidate therapeutic mouse and human neutralizing monoclonal antibodies (mAbs) target epitopes within the E domain III lateral ridge and the domain I-II hinge region, respectively . To explore the neutralizing antibody repertoire elicited by WNV infection for potential therapeutic application, we isolated ten mAbs from WNV-infected individuals. mAb WNV-86 neutralized WNV with a 50% inhibitory concentration of 2 ng ml , one of the most potently neutralizing flavivirus-specific antibodies ever isolated. WNV-86 targets an epitope in E domain II, and preferentially recognizes mature virions lacking an uncleaved form of the chaperone protein prM, unlike most flavivirus-specific antibodies . In vitro selection experiments revealed a neutralization escape mechanism involving a glycan addition to E domain II. Finally, a single dose of WNV-86 administered two days post-infection protected mice from lethal WNV challenge. This study identifies a highly potent human neutralizing mAb with therapeutic potential that targets an epitope preferentially displayed on mature virions.