Publication: Humanized monoclonal antibodies derived from chimpanzee fabs protect against Japanese encephalitis virus in vitro and in vivo
1
Issued Date
2008-07-01
Resource Type
ISSN
0022538X
Other identifier(s)
2-s2.0-47049117135
Rights
Mahidol University
Rights Holder(s)
SCOPUS
Bibliographic Citation
Journal of Virology. Vol.82, No.14 (2008), 7009-7021
Suggested Citation
Ana P. Goncalvez, Cheng Hsin Chien, Kamolchanok Tubthong, Inna Gorshkova, Carrie Roll, Olivia Donau, Peter Schuck, Sutee Yoksan, Sy Dar Wang, Robert H. Purcell, Ching Juh Lai Humanized monoclonal antibodies derived from chimpanzee fabs protect against Japanese encephalitis virus in vitro and in vivo. Journal of Virology. Vol.82, No.14 (2008), 7009-7021. doi:10.1128/JVI.00291-08 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/18725
Research Projects
Organizational Units
Authors
Journal Issue
Thesis
Title
Humanized monoclonal antibodies derived from chimpanzee fabs protect against Japanese encephalitis virus in vitro and in vivo
Abstract
Japanese encephalitis virus (JEV)-specific Fab antibodies were recovered by repertoire cloning from chimpanzees initially immunized with inactivated JE-VAX and then boosted with attenuated JEV SA14-14-2. 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 Lys179(domain I), that for Fab B2 was Ile126(domain II), and that for Fab E3 was Gly302(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 (ED50) of 0.84 μg, followed by MAb A3 (ED50of 5.8 μg) and then MAb E3 (ED50of 24.7 μg) for a 4-week-old mouse. Administration of 200 μg/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. Copyright © 2008, American Society for Microbiology. All Rights Reserved.