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Nat Commun. 2018 Apr 24;9(1):1624. doi: 10.1038/s41467-018-04056-4.

Fetal demise and failed antibody therapy during Zika virus infection of pregnant macaques.

Author information

1
Department of Pathology, University of Miami Leonard M. Miller School of Medicine, 1951 NW 7th Ave Room 2340, Miami, FL, 33136, USA.
2
Department of Immunology and Microbiology, The Scripps Research Institute, 3215 Merryfield Row Immunology 308, San Diego, CA, 92121, USA.
3
Tulane National Primate Research Center, 18703 Three Rivers Road, Covington, LA, 70433, USA.
4
Institute for Antiviral Research, Utah State University, 5600 Old Main Hill, Logan, UT, 84322-5600, USA.
5
Department of Obstetrics and Gynecology, University of Miami Leonard M. Miller School of Medicine, CRB 11th floor, Miami, FL, 33136, USA.
6
Division of Clinical Immunology and Allergy, School of Medicine, University of São Paulo, Av. Dr. Arnaldo 455, Terceiro andar, São Paulo, SP, 01246-903, Brazil.
7
Department of Medicine, University of Miami Leonard M. Miller School of Medicine, 1600 NW 10th Ave #1140, Miami, FL, USA.
8
Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bldg 33, Room 3W10A, 33 North Drive, MSC 3210, Bethesda, MD, 20892-3210, USA.
9
Scripps Translational Science Institute, 10550 North Torrey Pines Road, La Jolla, CA, 92037, USA.
10
Department of Integrative Structural and Computational Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, 92037, La Jolla, CA, USA.
11
Laboratório de Biologia Molecular de Flavivírus, Instituto Oswaldo Cruz, Fiocruz, Avenida Brasil, 4365, Manguinhos, Rio de Janeiro, RJ, 21040-360, Brazil.
12
Department of Immunology and Microbiology, The Scripps Research Institute, 3215 Merryfield Row Immunology 308, San Diego, CA, 92121, USA. burton@scripps.edu.
13
Ragon Institute, Harvard Medical School, 400 Technology Square, Cambridge, Boston, MA, 02139, USA. burton@scripps.edu.
14
Department of Pathology, University of Miami Leonard M. Miller School of Medicine, 1951 NW 7th Ave Room 2340, Miami, FL, 33136, USA. dwatkins@med.miami.edu.

Abstract

Zika virus (ZIKV) infection of pregnant women is associated with pathologic complications of fetal development. Here, we infect pregnant rhesus macaques (Macaca mulatta) with a minimally passaged ZIKV isolate from Rio de Janeiro, where a high rate of fetal development complications was observed. The infection of pregnant macaques with this virus results in maternal viremia, virus crossing into the amniotic fluid (AF), and in utero fetal deaths. We also treated three additional ZIKV-infected pregnant macaques with a cocktail of ZIKV-neutralizing human monoclonal antibodies (nmAbs) at peak viremia. While the nmAbs can be effective in clearing the virus from the maternal sera of treated monkeys, it is not sufficient to clear ZIKV from AF. Our report suggests that ZIKV from Brazil causes fetal demise in non-human primates (NHPs) without additional mutations or confounding co-factors. Treatment with a neutralizing anti-ZIKV nmAb cocktail is insufficient to fully stop vertical transmission.

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