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

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Abstract

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, a flavivirus closely related to ZIKV. Here we investigate the serological crossreaction between the two viruses. Dengue immune plasma substantially crossreacted with ZIKV and could drive antibody-dependent enhancement of ZIKV infection. Using a panel of human anti-dengue monoclonal antibodies we showed that most antibodies reacting to dengue envelope protein also reacted to ZIKV. Antibodies to linear epitopes including the immunodominant fusion loop epitope while able to bind ZIKV could not neutralize the virus but instead promoted ADE. These data indicate that dengue immunity may drive higher ZIKV replication and have clear implications for disease pathogenesis and future ZIKV and dengue vaccine programs.

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First report of autochthonous transmission of Zika virus in Brazil

Camila Zanluca, Vanessa de Melo, Ana Mosimann … (2015)

In the early 2015, several cases of patients presenting symptoms of mild fever, rash, conjunctivitis and arthralgia were reported in the northeastern Brazil. Although all patients lived in a dengue endemic area, molecular and serological diagnosis for dengue resulted negative. Chikungunya virus infection was also discarded. Subsequently, Zika virus (ZIKV) was detected by reverse transcription-polymerase chain reaction from the sera of eight patients and the result was confirmed by DNA sequencing. Phylogenetic analysis suggests that the ZIKV identified belongs to the Asian clade. This is the first report of ZIKV infection in Brazil.

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Research on dengue during World War II.

A SABIN (1952)

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A new class of highly potent, broadly neutralizing antibodies isolated from viremic patients infected with dengue virus.

Wanwisa Dejnirattisai, Wiyada Wongwiwat, Sunpetchuda Supasa … (2015)

Dengue is a rapidly emerging, mosquito-borne viral infection, with an estimated 400 million infections occurring annually. To gain insight into dengue immunity, we characterized 145 human monoclonal antibodies (mAbs) and identified a previously unknown epitope, the envelope dimer epitope (EDE), that bridges two envelope protein subunits that make up the 90 repeating dimers on the mature virion. The mAbs to EDE were broadly reactive across the dengue serocomplex and fully neutralized virus produced in either insect cells or primary human cells, with 50% neutralization in the low picomolar range. Our results provide a path to a subunit vaccine against dengue virus and have implications for the design and monitoring of future vaccine trials in which the induction of antibody to the EDE should be prioritized.