Preexisting immunity against dengue virus or West Nile virus was previously reported to mediate antibody-dependent enhancement (ADE) of Zika virus (
ZIKV) infection in a mouse model. We show here that ZIKV-immune plasma samples from both symptomatic and asymptomatic individuals mediated ZIKV ADE of
infection in vitro and in mice. In a lethal
infection model with a viral inoculum 10 times higher, both ADE and protection were observed, depending on the amount of infused immune plasma. In a vertical-transmission model, ZIKV-immune plasma infused to timed pregnant mice increased
fetal demise and decreased the
body weight of surviving fetuses. Depletion of
IgG from an immune plasma abolished ADE of
infection, and the presence of purified
IgG alone mediated ADE of
infection. Higher viral loads and proinflammatory
cytokines were detected in mice treated with ZIKV-immune plasma samples compared to those receiving control plasma. Together, these data show that passive immunization with homotypic ZIKV
antibodies, depending on the concentration, could either worsen or limit a subsequent
ZIKV infection.IMPORTANCE Antibody-dependent enhancement (ADE) of
virus infection is common to many viruses and is problematic when plasma antibody levels decline to subneutralizing concentrations. ADE of
infection is especially important among flaviviruses, many of which are the cause of global health problems. Recently, human plasma samples immune to heterologous flaviviruses were shown to promote Zika virus (
ZIKV) infection. Here we showed in immunocompromised mouse models that homologous immune plasma samples protect mice from subsequent
infection at high antibody concentrations but that they mediate ADE of
infection and increase ZIKV pathogenesis in adult mice and
fetal demise during pregnancy at low concentrations.