Publication: Characterization of a potent and highly unusual minimally enhancing antibody directed against dengue virus
Issued Date
2018-11-01
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ISSN
15292916
15292908
15292908
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2-s2.0-85055039332
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Mahidol University
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SCOPUS
Bibliographic Citation
Nature Immunology. Vol.19, No.11 (2018), 1248-1256
Suggested Citation
Max Renner, Aleksandra Flanagan, Wanwisa Dejnirattisai, Chunya Puttikhunt, Watchara Kasinrerk, Piyada Supasa, Wiyada Wongwiwat, Kriangkrai Chawansuntati, Thaneeya Duangchinda, Alison Cowper, Claire M. Midgley, Prida Malasit, Juha T. Huiskonen, Juthathip Mongkolsapaya, Gavin R. Screaton, Jonathan M. Grimes Characterization of a potent and highly unusual minimally enhancing antibody directed against dengue virus. Nature Immunology. Vol.19, No.11 (2018), 1248-1256. doi:10.1038/s41590-018-0227-7 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/45951
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Title
Characterization of a potent and highly unusual minimally enhancing antibody directed against dengue virus
Author(s)
Abstract
© 2018, The Author(s), under exclusive licence to Springer Nature America, Inc. Dengue virus is a major pathogen, and severe infections can lead to life-threatening dengue hemorrhagic fever. Dengue virus exists as four serotypes, and dengue hemorrhagic fever is often associated with secondary heterologous infections. Antibody-dependent enhancement (ADE) may drive higher viral loads in these secondary infections and is purported to result from antibodies that recognize dengue virus but fail to fully neutralize it. Here we characterize two antibodies, 2C8 and 3H5, that bind to the envelope protein. Antibody 3H5 is highly unusual as it not only is potently neutralizing but also promotes little if any ADE, whereas antibody 2C8 has strong capacity to promote ADE. We show that 3H5 shows resilient binding in endosomal pH conditions and neutralizes at low occupancy. Immunocomplexes of 3H5 and dengue virus do not efficiently interact with Fcγ receptors, which we propose is due to the binding mode of 3H5 and constitutes the primary mechanism of how ADE is avoided.