Two Zika Neutralizing Antibodies Found

Researchers have found two potent Zika-neutralizing antibodies that could be used as part of a therapeutic cocktail to treat patients.

AsianScientist (Dec. 28, 2016) – Researchers in China have isolated two antibodies that can neutralize the Zika virus without cross-reactivity to dengue viruses. Their results, published in Science Translational Medicine, demonstrate the therapeutic potential of monoclonal antibodies against Zika and provide a structure-based rationale for the design of future specific antivirals.

Zika virus (ZIKV) is a flavivirus that has caused widespread concern. Accumulating evidence suggests that infection is associated with microcephaly in newborns and neurological complications, such as Guillain-Barré syndrome, in adults. Zika is fortunately no longer considered an international public health emergency by the World Health Organization, but an urgent need for preventative and treatment approaches, none of which has been clinically approved, remains.

The ZIKV envelope protein is known to facilitate virus entry into the cell and contains important epitopes for virus neutralization. To isolate antibodies that bind to soluble envelope (sE) protein, the research groups of Professors Yan Jinghua and George Fu Gao from the Chinese Academy of Sciences screened peripheral blood mononuclear cells isolated from a patient recovering from a Zika infection.

After cell sorting for memory B cell markers, 33 sE-specific memory B cells were found. The sequences of 13 antibodies produced by the cells were cloned and produced as monoclonal antibodies. Of these 13, three (Z20, Z23 and Z3L1) were found to potently neutralize ZIKV. Furthermore, Z23 and Z3L1 showed no cross-binding or cross-neutralization to dengue virus serotypes 1-4, the closest phylogenetic relative to ZIKV.

When given to mice infected with ZIKV, both Z23 and Z3L1 conferred complete post-exposure protection whereas Z20 conferred partial protection. Structural studies revealed that Z20, Z23 and Z3L1 bound to tertiary epitopes on domains I, II and/or III of the envelope protein, and inhibit virus entry through different mechanisms.

The article can be found at: Wang et al. (2016) Molecular Determinants of Human Neutralizing Antibodies Isolated from a Patient Infected with Zika Virus.


Source: Chinese Academy of Sciences; Photo: Shutterstock.
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