Research ArticleZIKA VIRUS

Molecular determinants of human neutralizing antibodies isolated from a patient infected with Zika virus

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Science Translational Medicine  14 Dec 2016:
Vol. 8, Issue 369, pp. 369ra179
DOI: 10.1126/scitranslmed.aai8336

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Stopping Zika virus in its tracks

Zika virus is a global concern because of its association with fetal microcephaly and neurological complications, and there are no approved countermeasures. In new work, Wang et al. isolated 13 antibodies from a patient infected with Zika virus, two of which (Z3L1 and Z23) showed potent neutralizing activity without cross-reactivity to dengue virus strains 1 to 4. Moreover, the Z3L1 and Z23 antibodies conferred postexposure protection against Zika virus in a murine model. Structural studies indicated that the antibodies bound to different viral epitopes, suggesting that these antibodies could be used as a therapeutic cocktail.

Abstract

The 2015–2016 outbreak of Zika virus (ZIKV) disease has affected many countries and is a major public health concern. ZIKV is associated with fetal microcephaly and neurological complications, and countermeasures are needed to treat and prevent ZIKV infection. We report the isolation of 13 specific human monoclonal antibodies from a single patient infected with ZIKV. Two of the isolated antibodies (Z23 and Z3L1) demonstrated potent ZIKV-specific neutralization in vitro without binding or neutralizing activity against strains 1 to 4 of dengue virus, the closest relative to ZIKV. These two antibodies provided postexposure protection to mice in vivo. Structural studies revealed that Z23 and Z3L1 bound to tertiary epitopes in envelope protein domain I, II, or III, indicating potential targets for ZIKV-specific therapy. Our results suggest the potential of antibody-based therapeutics and provide a structure-based rationale for the design of future ZIKV-specific vaccines.

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