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

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 | Michael J Ricciardi | Tereance A Myers | Justin G Julander | Rudolf P Bohm | Margaret H Gilbert | Faith Schiro | Pyone P Aye | Robert V Blair | Mauricio A Martins | Kathrine P Falkenstein | Amitinder Kaur | Christine L Curry | Esper G Kallas | Ronald C Desrosiers | Pascal J Goldschmidt-Clermont | Stephen S Whitehead | Kristian G Andersen | Myrna C Bonaldo | Andrew A Lackner | Antonito T Panganiban | Dennis R Burton | David I Watkins
Nature communications | 2018

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.

Pubmed ID: 29691387

Associated grants

  • Agency: NIH HHS, United States
    Id: P51 OD011104
  • Agency: NIH HHS, United States
    Id: K01 OD023032
  • Agency: NIAID NIH HHS, United States
    Id: P30 AI073961
  • Agency: NIAID NIH HHS, United States
    Id: R21 AI137690
  • Agency: NIAID NIH HHS, United States
    Id: P01 AI094420
  • Agency: NIAID NIH HHS, United States
    Id: T32 AI007244
  • Agency: NIH HHS, United States
    Id: T32 OD011124

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