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Dengue Virus Antibodies Enhance Zika Virus Infection

Lauren M Paul, Eric R Carlin, Meagan M Jenkins, Amanda L Tan, Carolyn M Barcellona, Cindo O Nicholson, Lydie Trautmann, Scott F Michael, Sharon Isern
doi: https://doi.org/10.1101/050112
Lauren M Paul
Florida Gulf Coast University;
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Eric R Carlin
Florida Gulf Coast University;
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Meagan M Jenkins
Florida Gulf Coast University;
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Amanda L Tan
Florida Gulf Coast University;
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Carolyn M Barcellona
Florida Gulf Coast University;
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Cindo O Nicholson
Florida Gulf Coast University;
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Lydie Trautmann
Walter Reed Army Institute of Research
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Scott F Michael
Florida Gulf Coast University;
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Sharon Isern
Florida Gulf Coast University;
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  • For correspondence: sisern@fgcu.edu
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Abstract

Background For decades, human infections with Zika virus (ZIKV), a mosquito-transmitted flavivirus, were sporadic, associated with mild disease, and went underreported since symptoms were similar to other acute febrile diseases endemic in the same regions. Recent reports of severe disease associated with ZIKV, including Guillain-Barre syndrome and severe fetal abnormalities, have greatly heightened awareness. Given its recent history of rapid spread in immune naive populations, it is anticipated that ZIKV will continue to spread in the Americas and globally in regions where competent Aedes mosquito vectors are found. Globally, dengue virus (DENV) is the most common mosquito-transmitted human flavivirus and is both well-established and the source of outbreaks in areas of recent ZIKV introduction. DENV and ZIKV are closely related, resulting in substantial antigenic overlap. Through a mechanism known as antibody-dependent enhancement (ADE), anti-DENV antibodies can enhance the infectivity of DENV for certain classes of immune cells, causing increased viral production that correlates with severe disease outcomes. Similarly, ZIKV has been shown to undergo ADE in response to antibodies generated by other flaviviruses. However, response to DENV antibodies has not yet been investigated. Methodology / Principal Findings We tested the neutralizing and enhancing potential of well-characterized broadly neutralizing human anti-DENV monoclonal antibodies (HMAbs) and human DENV immune sera against ZIKV using neutralization and ADE assays. We show that anti-DENV HMAbs, cross-react, do not neutralize, and greatly enhance ZIKV infection in vitro. DENV immune sera had varying degrees of neutralization against ZIKV and similarly enhanced ZIKV infection. Conclusions / Significance Our results suggest that pre-existing DENV immunity will enhance ZIKV infection in vivo and may increase disease severity. A clear understanding of the interplay between ZIKV and DENV will be critical in informing public health responses in regions where these viruses co-circulate and will be particularly valuable for ZIKV and DENV vaccine design and implementation strategies.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted April 25, 2016.
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Dengue Virus Antibodies Enhance Zika Virus Infection
Lauren M Paul, Eric R Carlin, Meagan M Jenkins, Amanda L Tan, Carolyn M Barcellona, Cindo O Nicholson, Lydie Trautmann, Scott F Michael, Sharon Isern
bioRxiv 050112; doi: https://doi.org/10.1101/050112
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Dengue Virus Antibodies Enhance Zika Virus Infection
Lauren M Paul, Eric R Carlin, Meagan M Jenkins, Amanda L Tan, Carolyn M Barcellona, Cindo O Nicholson, Lydie Trautmann, Scott F Michael, Sharon Isern
bioRxiv 050112; doi: https://doi.org/10.1101/050112

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