2. Academic Validation
  3. A protective human monoclonal antibody targeting the West Nile virus E protein preferentially recognizes mature virions

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

  • Nat Microbiol. 2019 Jan;4(1):71-77. doi: 10.1038/s41564-018-0283-7.
Leslie Goo 1 2,  Kari Debbink 1,  Nurgun Kose 3,  Gopal Sapparapu 4,  Michael P Doyle 5,  Alex W Wessel 6,  Justin M Richner 6 7,  Katherine E Burgomaster 1,  Bridget C Larman 1,  Kimberly A Dowd 1,  Michael S Diamond 6,  James E Crowe Jr 8,  Theodore C Pierson 9
Affiliations

Affiliations

  • 1 Viral Pathogenesis Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
  • 2 Chan Zuckerberg Biohub, San Francisco, CA, USA.
  • 3 Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN, USA.
  • 4 Department of Pediatrics, and the Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN, USA.
  • 5 Department of Pathobiology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA.
  • 6 Departments of Medicine, Molecular Microbiology, Pathology and Immunology, and The Andrew M. and Jane M. Bursky Center for Human Immunology and Immunotherapy Programs, Washington University School of Medicine, St. Louis, MO, USA.
  • 7 Department of Microbiology and Immunology, University of Illinois at Chicago, Chicago, IL, USA.
  • 8 Departments of Pediatrics, Pathobiology, Microbiology and Immunology, and the Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN, USA. james.crowe@vanderbilt.edu.
  • 9 Viral Pathogenesis Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA. piersontc@niaid.nih.gov.
PMID: 30455471 DOI: 10.1038/s41564-018-0283-7
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.

Figures
Products
嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z