Isolation and Characterization of Human Monoclonal Antibodies from Individuals Infected with West Nile Virus Academic Article uri icon

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abstract

  • ABSTRACT Monoclonal antibodies (MAbs) neutralizing West Nile Virus (WNV) have been shown to protect against infection in animal models and have been identified as a correlate of protection in WNV vaccine studies. In the present study, antibody repertoires from three convalescent WNV-infected patients were cloned into an scFv phage library, and 138 human MAbs binding to WNV were identified. One hundred twenty-one MAbs specifically bound to the viral envelope (E) protein and four MAbs to the premembrane (prM) protein. Enzyme-linked immunosorbent assay-based competitive-binding assays with representative E protein-specific MAbs demonstrated that 24/51 (47%) bound to domain II while only 4/51 (8%) targeted domain III. In vitro neutralizing activity was demonstrated for 12 MAbs, and two of these, CR4374 and CR4353, protected mice from lethal WNV challenge at 50% protective doses of 12.9 and 357 μg/kg of body weight, respectively. Our data analyzing three infected individuals suggest that the human anti-WNV repertoire after natural infection is dominated by nonneutralizing or weakly neutralizing MAbs binding to domain II of the E protein, while domain III-binding MAbs able to potently neutralize WNV in vitro and in vivo are rare.

authors

  • Throsby, Mark
  • Geuijen, Cecile
  • Goudsmit, Jaap
  • Bakker, Arjen Q
  • Korimbocus, Jehanara
  • Kramer, R Arjen
  • Clijsters-van der Horst, Marieke
  • de Jong, Maureen
  • Jongeneelen, Mandy
  • Thijsse, Sandra
  • Smit, Renate
  • Visser, Therese J
  • Bijl, Nora
  • Marissen, Wilfred E
  • Loeb, Mark
  • Kelvin, David J
  • Preiser, Wolfgang
  • ter Meulen, Jan
  • de Kruif, John

publication date

  • July 15, 2006