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Neutralizing human monoclonal antibodies prevent Zika virus infection in macaques

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Science Translational Medicine  04 Oct 2017:
Vol. 9, Issue 410, eaan8184
DOI: 10.1126/scitranslmed.aan8184

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Antibodies provide promising Zika prophylaxis

The recent Zika virus epidemic and ensuing fetal consequences caught the world off guard. Scientists are now scrambling for information on Zika virus detection, treatment, and prevention. Passive immunity provided by monoclonal antibodies offers an attractive alternative to traditional vaccines, because it can be generated relatively quickly. Magnani et al. isolated and engineered three neutralizing antibodies from a Zika-infected patient. Administration of these antibodies completely protected nonhuman primates from becoming infected with Zika virus, suggesting that such a cocktail could be used to prevent Zika infections in people.

Abstract

Therapies to prevent maternal Zika virus (ZIKV) infection and its subsequent fetal developmental complications are urgently required. We isolated three potent ZIKV-neutralizing monoclonal antibodies (nmAbs) from the plasmablasts of a ZIKV-infected patient—SMZAb1, SMZAb2, and SMZAb5—directed against two different domains of the virus. We engineered these nmAbs with Fc LALA mutations that abrogate Fcγ receptor binding, thus eliminating potential therapy-mediated antibody-dependent enhancement. We administered a cocktail of these three nmAbs to nonhuman primates 1 day before challenge with ZIKV and demonstrated that the nmAbs completely prevented viremia in serum after challenge. Given that numerous antibodies have exceptional safety profiles in humans, the cocktail described here could be rapidly developed to protect uninfected pregnant women and their fetuses.

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