Isolation and Characterization of Human Monoclonal Antibodies from Individuals Infected with West Nile Virus
| Autor: | Renate Smit, Therese Visser, David J. Kelvin, Jaap Goudsmit, Nora Bijl, Marieke Clijsters-van der Horst, R. Arjen Kramer, Maureen de Jong, Mandy Jongeneelen, Cecile Geuijen, Mark Throsby, Mark Loeb, Jehanara Korimbocus, Arjen Q. Bakker, Jan ter Meulen, Sandra Thijsse, Wolfgang Preiser, John de Kruif, Wilfred E. Marissen |
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| Přispěvatelé: | Amsterdam institute for Infection and Immunity, General Internal Medicine, Medical Biochemistry |
| Rok vydání: | 2006 |
| Předmět: |
medicine.drug_class
viruses Immunology Biology Antibodies Viral Monoclonal antibody Microbiology Virus Mice Flaviviridae Viral Envelope Proteins Viral envelope Antibody Specificity In vivo Virology medicine Animals Humans Cloning Molecular Antibodies Monoclonal virus diseases biology.organism_classification In vitro Protein Structure Tertiary Flavivirus Insect Science biology.protein Pathogenesis and Immunity Binding Sites Antibody Antibody West Nile virus West Nile Fever |
| Zdroj: | Journal of virology, 80(14), 6982-6992. American Society for Microbiology |
| ISSN: | 1098-5514 0022-538X |
| DOI: | 10.1128/jvi.00551-06 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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