Improved Immune Responses Against Zika Virus After Sequential Dengue and Zika Virus Infection in Humans.

Félix Delgado,Claude Roth,Etienne Simon-Lorière,Karina Torres,Jaime Castellanos,Consuelo Romero-Sánchez,Anavaj Sakuntabhai

doi:10.3390/v10090480

Félix Delgado, Claude Roth + Show 5 more

Open Access

https://doi.org/10.3390/v10090480

Copy DOI

Abstract

The high levels of dengue-virus (DENV) seroprevalence in areas where the Zika virus (ZIKV) is circulating and the cross-reactivity between these two viruses have raised concerns on the risk of increased ZIKV disease severity for patients with a history of previous DENV infections. To determine the role of DENV preimmunity in ZIKV infection, we analyzed the T- and B-cell responses against ZIKV in donors with or without previous DENV infection. Using peripheral blood mononuclear cells (PBMCs) from donors living in an endemic area in Colombia, we have identified, by interferon (IFN)-γ enzyme-linked immunospot (ELISPOT) assay, most of the immunodominant ZIKV T-cell epitopes in the nonstructural (NS) proteins NS1, NS3, and NS5. Analyses of the T- and B-cell responses in the same donors revealed a stronger T-cell response against peptides conserved between DENV and ZIKV, with a higher level of ZIKV-neutralizing antibodies in DENV-immune donors in comparison with DENV-naïve donors. Strikingly, the potential for antibody-mediated enhancement of ZIKV infection was reduced in donors with sequential DENV and ZIKV infection in comparison with donors with DENV infection only. Altogether, these data suggest that individuals with DENV immunity present improved immune responses against ZIKV.

Highlights

The Zika virus (ZIKV) is a flavivirus transmitted by Aedes species mosquitoes
To investigate T-cell immunity induced after ZIKV infection, we examined responses from blood donors living in a ZIKV-endemic area in gamma interferon (IFN-γ)-specific enzyme-linked immunospot (ELISPOT) assays
With the exception of one donor showing high T-cell activity against NS3 and a moderate/low level of neutralizing antibodies, all the other ZIKV-immune DENV-naïve donors exhibited low T-cell activity and a moderate/low level of neutralizing antibodies. These results suggest that cross-reactive T cells, which are induced after a sequential DENV and ZIKV infection, and exhibit strong functional activity against specific ZIKV epitopes, could play a role in the induction of antibodies with high neutralizing potential against ZIKV

Summary

Introduction

The Zika virus (ZIKV) is a flavivirus transmitted by Aedes species mosquitoes. It is a single positive-stranded RNA virus closely related to the yellow-fever virus, dengue virus (DENV), and WestNile virus [1]. The Zika virus (ZIKV) is a flavivirus transmitted by Aedes species mosquitoes. It is a single positive-stranded RNA virus closely related to the yellow-fever virus, dengue virus (DENV), and West. Isolated in the Zika forest in Uganda in 1947 [2], it caused an explosive outbreak for the first time in Yap Island, Federated States of Micronesia in 2007 [3]. Initially believed to only cause mild, self-limiting disease, a causal relationship between ZIKV and neurological complications, such as Guillain-Barré syndrome or congenital malformations, was established during the 2013 and 2015 outbreaks in French.

Methods

Results

Conclusion