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Advances in the research and development of therapeutic antibodies against the Zika virus

Cellular & Molecular Immunology volume 16, pages 96–97 (2019)Cite this article

The Zika virus (ZIKV) is an arbovirus in the same family, Flaviviridae, as the dengue virus (DENV), the West Nile virus, the yellow fever virus, and the Japanese encephalitis virus. ZIKV has been a recent research focus because of its close association with severe human diseases and syndromes, particularly congenital Zika syndrome, which includes fetal microcephaly and other brain abnormalities.1 The ZIKV envelope (E) protein is a major structural protein involved in receptor binding, viral entry, and fusion. It is arranged as a dimer, with each monomer consisting of three domains (DI, DII, and DIII), a stem region, and a transmembrane region.2 The ZIKV E protein induces the production of potent neutralizing antibodies against ZIKV and is thus a key target for the development of therapeutic ZIKV antibodies.

Several ZIKV E-targeting monoclonal antibodies (mAbs) with therapeutic potential have been developed (Table 1). Except for one mAb, Tyzivumab, which is currently undergoing testing for safety and tolerability in Phase 1 clinical trials (https://clinicaltrials.gov/ct2/show/NCT03443830), these mAbs are in preclinical development. While E-targeting mAbs are typically tested for neutralizing activity against ZIKV in vitro, most have also been evaluated for in vivo protective efficacy in ZIKV-susceptible animal models, including type I interferon (IFN) receptor (Ifnar1)-deficient A129 mice, type I/II IFN receptor-deficient AG129 or AG6 mice, and non-human primates (NHPs).3,4,5,6 The mAbs mainly target the DI, DII, or DIII region of the ZIKV E protein. Depending on the mAb concentrations, virus titers, virus strains, and injection routes, as well as the animal models used for the neutralization evaluation and/or challenge studies, the protective efficacy of these mAbs against ZIKV may vary.

Table 1 Summary of preclinically developed ZIKV E-targeting neutralizing mAbs with therapeutic potential
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Authors and Affiliations

  1. Lindsley F. Kimball Research Institute, New York Blood Center, New York, NY, 10065, USA

    Shibo Jiang & Lanying Du

  2. Key Laboratory of Medical Molecular Virology, Ministries of Education and Health, Shanghai Medical College and Institute of Medical Microbiology, Fudan University, Shanghai, 200032, China

    Shibo Jiang

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  1. Shibo Jiang
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Jiang, S., Du, L. Advances in the research and development of therapeutic antibodies against the Zika virus. Cell Mol Immunol 16, 96–97 (2019). https://doi.org/10.1038/s41423-018-0043-x

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