Human antibodies to dengue virus have therapeutic potential against Zika virus

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Researchers have discovered that antibodies taken from dengue virus (DNV) infected individuals are effective in treating Zika virus (ZIKV) infection a closely related flavivirus in rodents.

The research team, led by experts from Imperial College London (UK) and Washington University (MO, USA), was part of an international collaboration. The goal was to build on previous findings that DENV-specific antibodies can neutralize ZIKV infection in cell culture.

The study, recently published in Nature Immunology, utilized a mouse model to demonstrate that antibodies against the DENV E-dimer epitope (EDE) effectively treat the early stages of ZIKV infection.

“This paper shows for the first time that antibodies we had previously found to be effective against dengue potently protect against Zika virus in mice and can treat the early stages of infection,” explained Gavin Screaton, senior author and Dean of the Faculty of Medicine at Imperial College London.

In trials, Zika-infected animals were treated with a single dose of the EDE1-B10 antibody 3 days post ZIKV infection and monitored for 21 days.

The researchers discovered that antibody treatment protected against lethality, and was associated with a reduced ZIKV level in brains and testes (sites known to be targeted by Zika) when compared with the control group.

Additionally, ZIKV burden in maternal and fetal tissues was reduced, and as a result, fetal demise was reduced from 90% to just 10%.

Previously, studies have demonstrated that DENV immunity might drive greater ZIKV replication and pathogenesis, by the mechanisms of antibody-dependent enhancement. A phenomenon whereby non-neutralizing antibodies adhere to ZIKV and instead of tagging particles for destruction, they facilitate virus entry into host immune cells.

The latest study however, proved that this problem can be overcome by modifying the proteins slightly to create a subgroup called anti-EDE1 antibodies.

According to the researchers, this study provides the ground work for a possible dual-Zika-dengue vaccine, if the findings can be replicated in primates.

Screaton added: “This group of antibodies is unique in being able to target dengue and Zika. The next step is to see whether they are effective in larger animal models, and potentially even humans.”

Sources: Fernandez E,  Dejnirattisai W, Cao B et al. Human antibodies to the dengue virus E-dimer epitope have therapeutic activity against Zika virus infection. Nat. Immunol. doi:10.1038/ni.3849 (2017); http://www3.imperial.ac.uk/newsandeventspggrp/imperialcollege/newssummary/news_25-9-2017-13-13-52

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