Time elapsed between Zika and dengue virus infections affects antibody and T cell responses

Erick X Pérez-Guzmán,Laura J White,Aravinda De Silva,Amelia K Pinto,Luis Giavedoni,Teresa Arana,Petraleigh Pantoja,Crisanta Serrano-Collazo,Daniela Weiskopf,Idia V Rodríguez,Mariah A Hassert,Vida Hodara,Laura Parodi,Alexandra Ortiz-Rosa,James D Brien,Carlos A Sariol,Lorna Cruz,Melween I Martínez

doi:10.1038/s41467-019-12295-2

Abstract

Zika virus (ZIKV) and dengue virus (DENV) are co-endemic in many parts of the world, but the impact of ZIKV infection on subsequent DENV infection is not well understood. Here we show in rhesus macaques that the time elapsed after ZIKV infection affects the immune response to DENV infection. We show that previous ZIKV exposure increases the magnitude of the antibody and T cell responses against DENV. The time interval between ZIKV and subsequent DENV infection further affects the immune response. A mid-convalescent period of 10 months after ZIKV infection results in higher and more durable antibody and T cell responses to DENV infection than a short period of 2 months. In contrast, previous ZIKV infection does not affect DENV viremia or pro-inflammatory status. Collectively, we find no evidence of a detrimental effect of ZIKV immunity in a subsequent DENV infection. This supports the implementation of ZIKV vaccines that could also boost immunity against future DENV epidemics.

Highlights

Zika virus (ZIKV) and dengue virus (DENV) are co-endemic in many parts of the world, but the impact of ZIKV infection on subsequent DENV infection is not well understood
The experimental design includes three cohorts of rhesus macaques (Macaca mulatta), within the age range considered as young adults (Supplementary Fig. 1k), that were challenged with DENV2 (NGC-44 strain), monitored, and bled for 3 months (Fig. 1)
Two cohorts were previously exposed to ZIKV: cohort 1 (ZIKVPF-10mo) was comprised of four animals that had been exposed to ZIKV H/PF/2013 strain 10 months before DENV-2 challenge, and cohort 2 (ZIKVPR-2mo) comprised of six animals that had been exposed to ZIKV PRVABC59 strain 2 months before DENV-2 challenge

Summary

Introduction

Zika virus (ZIKV) and dengue virus (DENV) are co-endemic in many parts of the world, but the impact of ZIKV infection on subsequent DENV infection is not well understood. We show in rhesus macaques that the time elapsed after ZIKV infection affects the immune response to DENV infection. The time interval between ZIKV and subsequent DENV infection further affects the immune response. We find no evidence of a detrimental effect of ZIKV immunity in a subsequent DENV infection. ZIKV established itself in tropical and sub-tropical regions that are endemic to other closely related flaviviruses such as dengue virus (DENV). Both viruses belong to the Flaviviridae family and are transmitted by. Due to the antigenic similarities between DENV and ZIKV, concerns have been raised regarding the impact of DENV–ZIKV cross-reactive immunity on the development of severe clinical manifestations[11,12].

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