Human Polyclonal Antibodies Prevent Lethal Zika Virus Infection in Mice

Emilie Branche,Ayo Yila Simon,Trevor Carnelley,Annie Elong Ngono,Nicholas Sheets,Anh-Viet Nguyen ,Kenneth S Kim ,Karla M Viramontes,Matthew P Young ,Mercylia Susantono ,José Ángel Regla-Nava ,Douglas C Barker ,Rebecca Salgado,Hongyu Qiu,Harpreet Sahota,Anila Mamidi,Joan M Valls Cuevas,Shantha Kodihalli,Kieron Kennedy,Sujan Shresta

doi:10.1038/s41598-019-46291-9

Emilie Branche, Ayo Yila Simon + Show 18 more

Open Access

https://doi.org/10.1038/s41598-019-46291-9

Copy DOI

Abstract

Zika virus (ZIKV) is an emerging mosquito-borne flavivirus that represents a major threat to global health. ZIKV infections in adults are generally asymptomatic or present with mild symptoms. However, recent outbreaks of ZIKV have revealed that it can cause Congenital Zika Syndrome in neonates and Guillain-Barré syndrome in adults. Currently, no ZIKV-specific vaccines or antiviral treatments are available. In this study, we tested the efficacy of convalescent plasma IgG hyperimmune product (ZIKV-IG) isolated from individuals with high neutralizing anti-ZIKV titers as a therapeutic candidate against ZIKV infection using a model of ZIKV infection in Ifnar1−/− mice. ZIKV-IG successfully protected mice from lethal ZIKV challenge. In particular, ZIKV-IG treatment at 24 hours after lethal ZIKV infection improved survival by reducing weight loss and tissue viral burden and improving clinical score. Additionally, ZIKV-IG eliminated ZIKV-induced tissue damage and inflammation in the brain and liver. These results indicate that ZIKV-IG is efficacious against ZIKV, suggesting this human polyclonal antibody is a viable candidate for further development as a treatment against human ZIKV infection.

Highlights

Zika virus (ZIKV) is an arthropod-borne virus belonging to the family Flaviviridae, similar to dengue, West Nile, Japanese encephalitis, and yellow fever viruses[1]
As no study has as yet assessed the efficacy of polyclonal antibodies (pAb) isolated from humans as a potential therapeutic against ZIKV, we evaluate the therapeutic potential of a pAb preparation from human plasma containing high anti-ZIKV titers (ZIKV-IG)
Vehicle control has been used as a negative control because the outcomes for animals treated with vehicle control were not significantly different to those observed in animals treated with a naïve-ZIKV-IG placebo, and significant differences were observed between 50 mg/kg ZIKV-IG treated mice and both vehicle control (p = 0.0022) and naïve-ZIKV-IG (p = 0.0022) treated mice (Supplementary Fig. S2 and Table S1)

Summary

Introduction

Zika virus (ZIKV) is an arthropod-borne virus belonging to the family Flaviviridae, similar to dengue, West Nile, Japanese encephalitis, and yellow fever viruses[1]. ZIKV evades the anti-viral type I interferon (IFN) response, in part through inhibition of the STAT2 and STING pathways in human but not mouse cells[48,49,50] This antagonism of the type I IFN receptor (Ifnar) signaling in a species-specific manner by ZIKV explains the more severe pathogenesis of ZIKV infection in mice with immature or compromised immune systems compared to adult immunocompetent mice, and why disruption of the Ifnar[1] signaling increases susceptibility of mice to lethal ZIKV infection. ZIKV-IG treatment at 24 hrs post-infection increased survival by reducing viral burden and ZIKV-induced tissue damage and inflammation in several key organs These findings demonstrated that a single dose of ZIKV-IG is efficacious against lethal Zika disease in a highly stringent mouse challenge model

Methods

Results

Conclusion