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May 8, 2018

Responding To: Addressing Pandemics and Global Migration

Neutralizing and Protective Human Antibodies Against Zika Virus Infection

Professor Zhang Linqi, Tsinghua University

Zika virus (ZIKV) is a mosquito-transmitted flavivirus that is generally benign in humans. However, a newly emergent strain of ZIKV has become widespread, causing severe pre- and post-natal neurological defects. Most notable was the recent unprecedented outbreaks in the Americas, Caribbean and Southeast Asia through the invasive mosquito species Aedes aegypti, although the underlying biological and ecological mechanisms remain unclear. The high prevalence of this mosquito species coupled with climate change is likely to fuel global spread of the epidemic, raising serious concerns about the pandemic potential of ZIKV in the near future.  However, no prophylactic and therapeutic agents are available against ZIKV infection.  During the ZIKV outbreak, we set out to isolate human monoclonal antibodies from two ZIKV-infected and convalescent Chinese who returned to China from traveling in two severely affected South American countries, Venezuela and Surinam.  Isolated antibodies demonstrated a great deal of variability in their activities against ZIKV, among which, we have identified a potent antibody, ZK2B10, which provided 100% protection from lethal ZIKV infection and microcephaly in mice. By crystal structure determination, the epitope of this star antibody targeted a unique spot on the viral envelope protein critical for ZIKV entry into the host cells.  Thus, ZK2B10 is a promising candidate for the development of antibody-based interventions and also provides critical reference for the rational design of ZIKV vaccine. We are in the process of developing this antibody for human studies in the near future.

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