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Sci Transl Med. 2017 Oct 4;9(410). pii: eaan8184. doi: 10.1126/scitranslmed.aan8184.

Neutralizing human monoclonal antibodies prevent Zika virus infection in macaques.

Author information

1
Department of Pathology, University of Miami Leonard M. Miller School of Medicine, Miami, FL 33136, USA.
2
Department of Immunology and Microbiology and International AIDS Vaccine Initiative Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA.
3
Division of Clinical Immunology and Allergy, School of Medicine, University of São Paulo, São Paulo, São Paulo, Brazil.
4
Yerkes National Primate Research Center, Emory University, Atlanta, GA 30329, USA.
5
Department of Pediatrics, Emory University, Atlanta, GA 30322, USA.
6
Laboratório de Biologia Molecular de Flavivírus, Instituto Oswaldo Cruz, Fiocruz, Rio de Janeiro 21040-360, Brazil.
7
Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
8
Department of Immunology and Microbiology and International AIDS Vaccine Initiative Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA. burton@scripps.edu dwatkins@med.miami.edu.
9
Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA.
10
Department of Pathology, University of Miami Leonard M. Miller School of Medicine, Miami, FL 33136, USA. burton@scripps.edu dwatkins@med.miami.edu.

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.

PMID:
28978754
PMCID:
PMC6155977
DOI:
10.1126/scitranslmed.aan8184
[Indexed for MEDLINE]
Free PMC Article

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