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From a panel of 11 Fabs recovered by different panning strategies, three highly potent neutralizing antibodies, termed Fabs A3, B2, and E3, which recognized spatially separated regions on the virion, were identified. These antibodies reacted with epitopes in different domains: the major determinant for Fab A3 was Lys<jats:sub>179<\/jats:sub>(domain I), that for Fab B2 was Ile<jats:sub>126<\/jats:sub>(domain II), and that for Fab E3 was Gly<jats:sub>302<\/jats:sub>(domain III) in the envelope protein, suggesting that these antibodies neutralize the virus by different mechanisms. Potent neutralizing antibodies reacted with a low number of binding sites available on the virion. These three Fabs and derived humanized monoclonal antibodies (MAbs) exhibited high neutralizing activities against a broad spectrum of JEV genotype strains. Demonstration of antibody-mediated protection of JEV infection in vivo is provided using the mouse encephalitis model. MAb B2 was most potent, with a 50% protective dose (ED<jats:sub>50<\/jats:sub>) of 0.84 \u03bcg, followed by MAb A3 (ED<jats:sub>50<\/jats:sub>of 5.8 \u03bcg) and then MAb E3 (ED<jats:sub>50<\/jats:sub>of 24.7 \u03bcg) for a 4-week-old mouse. Administration of 200 \u03bcg\/mouse of MAb B2 1 day after otherwise lethal JEV infection protected 50% of mice and significantly prolonged the average survival time compared to that of mice in the unprotected group, suggesting a therapeutic potential for use of MAb B2 in humans.<\/jats:p>","DOI":"10.1128\/jvi.00291-08","type":"journal-article","created":{"date-parts":[[2008,5,15]],"date-time":"2008-05-15T01:39:34Z","timestamp":1210815574000},"page":"7009-7021","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":69,"title":["Humanized Monoclonal Antibodies Derived from Chimpanzee Fabs Protect against Japanese Encephalitis Virus In Vitro and In Vivo"],"prefix":"10.1128","volume":"82","author":[{"given":"Ana P.","family":"Goncalvez","sequence":"first","affiliation":[{"name":"Molecular Viral Biology Section"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cheng-Hsin","family":"Chien","sequence":"additional","affiliation":[{"name":"Adimmune Corporation, Taichung, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kamolchanok","family":"Tubthong","sequence":"additional","affiliation":[{"name":"Institute of Science and Technology for Research and Development, Mahidol University, Nakhonpathom, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Inna","family":"Gorshkova","sequence":"additional","affiliation":[{"name":"Protein Biophysics, National Institute of Biomedical Imaging and Bioengineering, NIH, Bethesda, Maryland 20892"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carrie","family":"Roll","sequence":"additional","affiliation":[{"name":"Molecular Viral Biology Section"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Olivia","family":"Donau","sequence":"additional","affiliation":[{"name":"Molecular Viral Biology Section"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter","family":"Schuck","sequence":"additional","affiliation":[{"name":"Protein Biophysics, National Institute of Biomedical Imaging and Bioengineering, NIH, Bethesda, Maryland 20892"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sutee","family":"Yoksan","sequence":"additional","affiliation":[{"name":"Institute of Science and Technology for Research and Development, Mahidol University, Nakhonpathom, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sy-Dar","family":"Wang","sequence":"additional","affiliation":[{"name":"Adimmune Corporation, Taichung, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert H.","family":"Purcell","sequence":"additional","affiliation":[{"name":"Hepatitis Viruses Section, Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ching-Juh","family":"Lai","sequence":"additional","affiliation":[{"name":"Molecular Viral Biology Section"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1348-0421.1997.tb01196.x"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.75.9.4268-4275.2001"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1348-0421.2007.tb03948.x"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1099\/0022-1317-67-2-229"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.4269\/ajtmh.1992.47.61"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.75.16.7769-7773.2001"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.virol.2005.04.031"},{"key":"e_1_3_2_9_2","doi-asserted-by":"crossref","first-page":"893","DOI":"10.4049\/jimmunol.154.2.893","volume":"154","year":"1995","unstructured":"Ditzel, H. 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