Journal Article

Dengue virus antibodies enhance Zika virus infection

Tan, Amanda L, Paul, Lauren M, Isern, Sharon, Barcellona, Carolyn M, Carlin, Eric R, Nicholson, Cindo O, Michael, Scott F, Jenkins, Meagan M

2016

Overview

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. Recent reports of severe disease associated with ZIKV have greatly heightened awareness. It is anticipated that ZIKV will continue to spread in the Americas and globally where competent Aedes mosquito vectors are found. Dengue virus (DENV), the most common mosquito‐transmitted human flavivirus, 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 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. 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. Our results suggest that pre‐existing DENV immunity may enhance ZIKV infection in vivo and may lead to increased disease severity. Understanding the interplay between ZIKV and DENV will be critical in informing public health responses and will be particularly valuable for ZIKV and DENV vaccine design and implementation strategies. Zika virus: A downside to defense against dengue Antibodies elicited by the dengue virus may contribute to more efficient infection by the Zika virus, resulting in more severe disease. Immune responses generated by an infection or vaccine may also protect against other closely related pathogens–but not always. Sharon Isern and Scott Michael at Florida Gulf Coast University and colleagues have found that some antibodies against the dengue virus actually promote Zika infection through a process of ‘antibody‐dependent enhancement’ (ADE). ADE has been observed in patients exposed to multiple subtypes of dengue virus, and researchers hypothesized that the same effect may occur with Zika virus, which belongs to the same viral family. They confirmed that antibodies from various dengue fever patients promoted infection of cultured immune cells by multiple Zika virus strains. These findings could have important implications for efforts to develop vaccines against both infections.

• Publisher: Nature Publishing Group,John Wiley & Sons, Inc
• Subject: Antisera / Dengue fever / Dengue virus / Disease / Epidemics / Immunoglobulins / Infections / Infectivity / Microcephaly / Monoclonal antibodies / Mosquitoes / Original / Outbreaks / Public health / Variance analysis / Vectors / Zika virus