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

Author

Listed:
  • Diogo M. Magnani

    (University of Miami Leonard M. Miller School of Medicine)

  • Thomas F. Rogers

    (The Scripps Research Institute)

  • Nicholas J. Maness

    (Tulane National Primate Research Center)

  • Nathan D. Grubaugh

    (The Scripps Research Institute)

  • Nathan Beutler

    (The Scripps Research Institute)

  • Varian K. Bailey

    (University of Miami Leonard M. Miller School of Medicine)

  • Lucas Gonzalez-Nieto

    (University of Miami Leonard M. Miller School of Medicine)

  • Martin J. Gutman

    (University of Miami Leonard M. Miller School of Medicine)

  • Núria Pedreño-Lopez

    (University of Miami Leonard M. Miller School of Medicine)

  • Jaclyn M. Kwal

    (University of Miami Leonard M. Miller School of Medicine)

  • Michael J. Ricciardi

    (University of Miami Leonard M. Miller School of Medicine)

  • Tereance A. Myers

    (Tulane National Primate Research Center)

  • Justin G. Julander

    (Utah State University)

  • Rudolf P. Bohm

    (Tulane National Primate Research Center)

  • Margaret H. Gilbert

    (Tulane National Primate Research Center)

  • Faith Schiro

    (Tulane National Primate Research Center)

  • Pyone P. Aye

    (Tulane National Primate Research Center)

  • Robert V. Blair

    (Tulane National Primate Research Center)

  • Mauricio A. Martins

    (University of Miami Leonard M. Miller School of Medicine)

  • Kathrine P. Falkenstein

    (Tulane National Primate Research Center)

  • Amitinder Kaur

    (Tulane National Primate Research Center)

  • Christine L. Curry

    (University of Miami Leonard M. Miller School of Medicine)

  • Esper G. Kallas

    (University of São Paulo)

  • Ronald C. Desrosiers

    (University of Miami Leonard M. Miller School of Medicine)

  • Pascal J. Goldschmidt-Clermont

    (University of Miami Leonard M. Miller School of Medicine)

  • Stephen S. Whitehead

    (National Institutes of Health)

  • Kristian G. Andersen

    (The Scripps Research Institute
    Scripps Translational Science Institute
    The Scripps Research Institute)

  • Myrna C. Bonaldo

    (Instituto Oswaldo Cruz, Fiocruz)

  • Andrew A. Lackner

    (Tulane National Primate Research Center)

  • Antonito T. Panganiban

    (Tulane National Primate Research Center)

  • Dennis R. Burton

    (The Scripps Research Institute
    Harvard Medical School)

  • David I. Watkins

    (University of Miami Leonard M. Miller School of Medicine)

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.

Suggested Citation

  • Diogo M. Magnani & Thomas F. Rogers & Nicholas J. Maness & Nathan D. Grubaugh & Nathan Beutler & Varian K. Bailey & Lucas Gonzalez-Nieto & Martin J. Gutman & Núria Pedreño-Lopez & Jaclyn M. Kwal & Mic, 2018. "Fetal demise and failed antibody therapy during Zika virus infection of pregnant macaques," Nature Communications, Nature, vol. 9(1), pages 1-8, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-04056-4
    DOI: 10.1038/s41467-018-04056-4
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