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Nat Immunol. 2016 Sep;17(9):1102-8. doi: 10.1038/ni.3515. Epub 2016 Jun 23.

Dengue virus sero-cross-reactivity drives antibody-dependent enhancement of infection with zika virus.

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Division of Immunology and Inflammation, Department of Medicine, Hammersmith Campus, Imperial College London, UK.
Dengue Hemorrhagic Fever Research Unit, Office for Research and Development, Siriraj Hospital, Faculty of Medicine, Mahidol University, Bangkok, Thailand.
Graduate Program in Immunology, Department of Immunology, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand.
Institut Pasteur, Département de Virologie, Unité de Virologie Structurale, Paris, France.
CNRS UMR 3569 Virologie, Paris, France.
Medical Biotechnology Unit, National Center for Genetic Engineering and Biotechnology, National Science and Technology Development Agency, Pathumthani, Thailand.
Institut Pasteur, Functional Genetics of Infectious Diseases Unit, Paris, France.
CNRS URA3012, Paris, France.
Unit of Emerging Infectious Diseases, Institut Louis Malardé, Papeete, Tahiti, French Polynesia.


Zika virus (ZIKV) was discovered in 1947 and was thought to lead to relatively mild disease. The recent explosive outbreak of ZIKV in South America has led to widespread concern, with reports of neurological sequelae ranging from Guillain Barré syndrome to microcephaly. ZIKV infection has occurred in areas previously exposed to dengue virus (DENV), a flavivirus closely related to ZIKV. Here we investigated the serological cross-reaction between the two viruses. Plasma immune to DENV showed substantial cross-reaction to ZIKV and was able to drive antibody-dependent enhancement (ADE) of ZIKV infection. Using a panel of human monoclonal antibodies (mAbs) to DENV, we showed that most antibodies that reacted to DENV envelope protein also reacted to ZIKV. Antibodies to linear epitopes, including the immunodominant fusion-loop epitope, were able to bind ZIKV but were unable to neutralize the virus and instead promoted ADE. Our data indicate that immunity to DENV might drive greater ZIKV replication and have clear implications for disease pathogenesis and future vaccine programs for ZIKV and DENV.

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Conflict of interest statement

The EDE antibodies and epitope are the subject of a patent application by Imperial College and Institute Pasteur on which G.S., F.R., A.R. and G.B.S. are named as inventors

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