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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 \u03bcg\/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.<\/jats:p>","DOI":"10.1128\/jvi.00551-06","type":"journal-article","created":{"date-parts":[[2006,6,28]],"date-time":"2006-06-28T22:27:07Z","timestamp":1151533627000},"page":"6982-6992","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":147,"title":["Isolation and Characterization of Human Monoclonal Antibodies from Individuals Infected with West Nile Virus"],"prefix":"10.1128","volume":"80","author":[{"given":"Mark","family":"Throsby","sequence":"first","affiliation":[{"name":"Crucell Holland B.V., Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cecile","family":"Geuijen","sequence":"additional","affiliation":[{"name":"Crucell Holland B.V., Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaap","family":"Goudsmit","sequence":"additional","affiliation":[{"name":"Crucell Holland B.V., Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arjen Q.","family":"Bakker","sequence":"additional","affiliation":[{"name":"Crucell Holland B.V., Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jehanara","family":"Korimbocus","sequence":"additional","affiliation":[{"name":"National Reference Center for Arbovirus and Viral Hemorrhagic Fevers, Pasteur Institute, Lyon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R. 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