Neutralizing human monoclonal antibodies prevent Zika virus infection in macaques

Diogo M. Magnani(University of Miami), Thomas F. Rogers(International AIDS Vaccine Initiative), Nathan Beutler(International AIDS Vaccine Initiative), Michael J. Ricciardi(University of Miami), Varian K. Bailey(University of Miami), Lucas Gonzalez-Nieto(University of Miami), Bryan Briney(International AIDS Vaccine Initiative), Devin Sok(International AIDS Vaccine Initiative), Khoa Le(International AIDS Vaccine Initiative), Alexander Strubel(International AIDS Vaccine Initiative), Martin J. Gutman(University of Miami), Núria Pedreño-López(University of Miami), Nathan D. Grubaugh(International AIDS Vaccine Initiative), Cássia Gisele Terrassani Silveira(Universidade Federal de São Paulo), Helen S. Maxwell(University of Miami), Aline Domingues(University of Miami), Maurício A. Martins(University of Miami), David E. Lee(Emory University), Erica Okwuazi(Emory University), Sherrie Jean(Emory University), Elizabeth Strobert(Emory University), Ann Chahroudi(Emory University), Guido Silvestri(Emory University), Thomas H. Vanderford(Emory University), Esper G. Kallás(Universidade Federal de São Paulo), Ronald C. Desrosiers(University of Miami), Myrna C. Bonaldo(Fundação Oswaldo Cruz), Stephen S. Whitehead(National Institutes of Health), Dennis R. Burton(International AIDS Vaccine Initiative), David I. Watkins(University of Miami)
Science Translational Medicine
October 4, 2017
10.1126/scitranslmed.aan8184
Cited by 99Open Access
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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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