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Article
Humanized Monoclonal Antibody against West Nile Virus Envelope Protein Administered after Neuronal Infection Protects against Lethal Encephalitis in Hamsters
The Journal of Infectious Diseases
  • John D. Morrey, Utah State University
  • V. Siddharthan
  • Aaron L. Olsen, Utah State University
  • G. Y. Roper
  • H. Wang
  • Thomas J. Baldwin, Utah State University
  • S. Koenig
  • S. Johnson
  • J. L. Nordstrom
  • M. S. Diamond
Document Type
Article
Publisher
University of Chicago Press
Publication Date
1-1-2006
DOI
10.1086/508293
Disciplines
Abstract
Humans infected with West Nile virus (WNV) may clinically present with symptoms that are suggestive of neurological infection. Nearly all treatments of WNV disease have been effective in animal models only if administered before or soon after viral challenge. Here, we evaluated whether a potent neutralizing anti-WNV humanized monoclonal antibody (MAb), hE16, could improve the course of disease in a hamster model when administered after the virus had infected neurons in the brain. Five days after viral injection, WNV was detected in the brains of hamsters by cytopathic assay, quantitative reverse-transcription polymerase chain reaction, and immunohistochemical staining of WNV envelope in neurons. Notably, 80%–90% of the hamsters treated 5 days after viral injection by intraperitoneal injection with hE16 survived the disease, compared with 37% of the placebo-treated hamsters (P <= .001). The hamsters that received hE16 directly in the brain also exhibited markedly improved survival rates, compared with those in the placebo-treated hamsters. In prospective experiments, hamsters with high levels of infectious WNV in their cerebrospinal fluid were also protected by hE16 when administered 5 days after viral injection. These experiments suggest that humanized MAbs with potent neutralizing activity are a possible treatment for human patients after WNV has infected neurons in the central nervous system.
Citation Information
Morrey, J.D., V. Siddharthan, A..L. Olsen, G.Y. Roper, H. Wang, T.J. Baldwin, S. Koenig, S. Johnson, J.L. Nordstrom, and M.S. Diamond 2006. Humanized monoclonal antibody against West Nile virus Envelope protein administered after neuronal infection protects against lethal encephalitis in hamsters. The Journal of Infectious Diseases 194: 1300-8.