Utility of a Dengue-Derived Monoclonal Antibody to Enhance Zika Infection In Vitro

Abstract

Introduction: Zika virus (ZIKV) has emerged in dengue (DENV) endemic areas, where these two related flaviviruses continue to co-circulate. DENV is a complex of four serotypes and infections can progress to severe disease. It is thought that this is mediated by antibody dependent enhancement (ADE) whereby antibodies from a primary DENV infection are incapable of neutralizing heterologous DENV infections with another serotype. ADE has been demonstrated among other members of the Flavivirus group.Methods: We utilize an in vitro ADE assay developed for DENV to determine whether ZIKV is enhanced by a commonly available DENV serotype 2-derived monoclonal antibody (4G2).Results: We show that ZIKV infection in vitro is enhanced in the presence of the 4G2 mAb.Discussion: Our results demonstrate that ADE between ZIKV and DENV is possible and that the 4G2 antibody is a useful tool for the effects of pre-existing anti-DENV antibodies during ZIKV infections.

Zika Virus Pathogenesis and Tissue Tropism

“…These cross-reactive antibodies have implications for ZIKV vaccine design, as they could result in exacerbated disease with subsequent DENV infection. Indeed, cross-reactive anti-DENV antibodies can enhance ZIKV infection in cell culture (Charles and Christofferson, 2016; Dejnirattisai et al, 2016; Priyamvada et al, 2016) and reciprocally, cross-reactive human anti-ZIKV antibodies can enhance DENV infection in cell culture and in mice (Stettler et al, 2016). However, at present, it remains unknown whether ADE of ZIKV infection by anti-DENV antibodies occurs in humans or other experimental animal models.…”

Zika Virus Persistence in the Central Nervous System and Lymph Nodes of Rhesus Monkeys

“…Adaptive immune control of ZIKV has been demonstrated by the capacity of virus-specific neutralizing antibodies to prevent and control infection in adoptive transfer studies in mice and monkeys (Abbink et al, 2016; Barouch et al, 2017; Larocca et al, 2016; Sapparapu et al, 2016). Cross-reactive antibodies with other flaviviruses such as dengue virus have also been described, although the potential clinical relevance of these cross-reactive antibodies remains to be determined (Barba-Spaeth et al, 2016; Charles and Christofferson, 2016; Dejnirattisai et al, 2016; Stettler et al, 2016). …”

Prospects for a Zika Virus Vaccine

“…Recently, a potent neutralizing antibody, ZIKV-117, directed against a quaternary epitope on the ZIKV envelope (Env) protein dimer-dimer interface was shown to block ZIKV infection in mice and to limit early viral replication and fetal pathology when administered following ZIKV infection of pregnant mice (Sapparapu et al, 2016). Cross-reactive neutralizing antibodies against ZIKV and DENV have also been shown to bind conserved epitopes on the two viruses and have been shown to enhance viral replication in vitro (Charles and Christofferson, 2016; Dejnirattisai et al, 2016) and in mice (Stettler et al, 2016), raising the possibility that such cross-reactive antibodies might have the potential for antibody-dependent enhancement of disease.…”

“…Recent studies have shown that DENV-specific sera and monoclonal antibodies can increase ZIKV replication both in vitro (Barba-Spaeth et al, 2016; Charles and Christofferson, 2016; Dejnirattisai et al, 2016) and in mice (Stettler et al, 2016). However, passive transfer of sub-protective doses of neutralizing antibodies prior to ZIKV challenge did not result in enhancement of ZIKV replication or disease in mice or monkeys (Abbink et al, 2016; Larocca et al, 2016).…”