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A protective human monoclonal antibody targeting the West Nile virus E protein preferentially recognizes mature virions
- Source :
- Nature Microbiology. 4:71-77
- Publication Year :
- 2018
- Publisher :
- Springer Science and Business Media LLC, 2018.
-
Abstract
- West Nile virus (WNV), a member of the Flavivirus genus, is a leading cause of viral encephalitis in the United States1. The development of neutralizing antibodies against the flavivirus envelope (E) protein is critical for immunity and vaccine protection2. 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, respectively3. 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-1, 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 antibodies4. 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. One of the most potently neutralizing flavivirus-specific monoclonal antibodies ever isolated, WNV-86, targets an epitope in E domain II of the West Nile virus (WNV), preferentially recognizes mature virions lacking an uncleaved form of the prM chaperone protein and protects mice from lethal WNV challenge when administered two days after infection.
- Subjects :
- Microbiology (medical)
medicine.drug_class
viruses
Immunology
Biology
Monoclonal antibody
Applied Microbiology and Biotechnology
Microbiology
Epitope
Neutralization
03 medical and health sciences
Immunity
Genetics
medicine
Neutralizing antibody
030304 developmental biology
0303 health sciences
030306 microbiology
virus diseases
Cell Biology
biology.organism_classification
Virology
nervous system diseases
3. Good health
Flavivirus
biology.protein
Vero cell
Antibody
Subjects
Details
- ISSN :
- 20585276
- Volume :
- 4
- Database :
- OpenAIRE
- Journal :
- Nature Microbiology
- Accession number :
- edsair.doi...........96b58390ad987a3c9162ab431e401879