Journal
NATURE IMMUNOLOGY
Volume 19, Issue 11, Pages 1248-+Publisher
NATURE PORTFOLIO
DOI: 10.1038/s41590-018-0227-7
Keywords
-
Categories
Funding
- Wellcome Trust, UK
- Newton-Medical Research Council, UK [MR/NO12658/2]
- National Institute for Health Research Oxford Biomedical Research Centre funding scheme
- Thailand National Center for Genetic Engineering
- and Biotechnology
- Academy of Finland
- Office of the Higher Education Commission
- Mahidol University under the National Research Universities Initiative
- Research Chair Grant from the National Science and Technology Development Agency (NSTDA), Thailand
- Faculty of Medicine Siriraj Hospital, Mahidol University [(IO)R015936005]
- Wellcome Trust [060208/Z/00/Z, 093305/Z/10/Z, 075491/Z/04, 095541/Z/11/Z, 203224/Z/16/Z, 204703/Z/16/Z, 080721/Z/06/Z]
- Wellcome Trust [204703/Z/16/Z, 203224/Z/16/Z, 095541/Z/11/Z, 080721/Z/06/Z] Funding Source: Wellcome Trust
Ask authors/readers for more resources
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 Fc gamma receptors, which we propose is due to the binding mode of 3H5 and constitutes the primary mechanism of how ADE is avoided.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available