Abstract
Zika virus is a mosquito-borne flavivirus closely related to dengue virus that can cause severe disease in humans, including microcephaly in newborns and Guillain-Barré syndrome in adults. Specific treatments and vaccines for Zika virus are not currently available. Here, we isolate and characterize four monoclonal antibodies (mAbs) from an infected patient that target the non-structural protein NS1. We show that while these antibodies are non-neutralizing, NS1-specific mAbs can engage FcγR without inducing antibody dependent enhancement (ADE) of infection in vitro. Moreover, we demonstrate that mAb AA12 has protective efficacy against lethal challenges of African and Asian lineage strains of Zika virus in Stat2–/– mice. Protection is Fc-dependent, as a mutated antibody unable to activate known Fc effector functions or complement is not protective in vivo. This study highlights the importance of the ZIKV NS1 protein as a potential vaccine antigen.
Highlights
Zika virus is a mosquito-borne flavivirus closely related to dengue virus that can cause severe disease in humans, including microcephaly in newborns and Guillain-Barré syndrome in adults
To investigate the antibody response to Zika virus (ZIKV) infection, we obtained plasma and isolated peripheral blood mononuclear cells (PBMCs) from a patient who was infected with ZIKV while traveling in Central America
We tested whether our antibodies bound by enzyme-linked immunosorbent assay (ELISA) to recombinant non-structural 1 (NS1) protein (Fig. 1b, c)
Summary
Zika virus is a mosquito-borne flavivirus closely related to dengue virus that can cause severe disease in humans, including microcephaly in newborns and Guillain-Barré syndrome in adults. 6 Division of Infectious Diseases, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA. To understand the molecular determinants of immunity to ZIKV infection, several groups have isolated monoclonal antibodies (mAbs) from patients infected with ZIKV8–12 These studies have revealed important antigenic sites on the envelope (E) protein required for virus neutralization. In a recent study of four patients infected by ZIKV, 34.4% of virus-specific mAbs target the NS1 protein[8] This immunogenic glycoprotein plays an essential role in viral RNA replication and immune evasion. An NS1-based vaccine for Zika virus was successfully tested in a mouse challenge model, proving that NS1mediated immunity alone is sufficient for a protective vaccine[32] These studies in many related flaviviruses suggest mAbs against the ZIKV NS1 protein are likely protective. We plan to determine if NS1-specific mAbs can provide protection in a murine model and whether this protection relies upon Fcγreceptor effector functions
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