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Title: Characterization of a potent and highly unusual minimally enhancing antibody directed against dengue virus
Authors: 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
Diamond Light Source
Wellcome Trust Centre for Human Genetics
Faculty of Medicine, Siriraj Hospital, Mahidol University
Nuffield Department of Clinical Medicine
Chiang Mai University
Keywords: Immunology and Microbiology;Medicine
Issue Date: 1-Nov-2018
Citation: Nature Immunology. Vol.19, No.11 (2018), 1248-1256
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.
ISSN: 15292916
Appears in Collections:Scopus 2018

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