TY - JOUR
T1 - Fetal demise and failed antibody therapy during Zika virus infection of pregnant macaques
AU - Magnani, Diogo M.
AU - Rogers, Thomas F.
AU - Maness, Nicholas J.
AU - Grubaugh, Nathan D.
AU - Beutler, Nathan
AU - Bailey, Varian K.
AU - Gonzalez-Nieto, Lucas
AU - Gutman, Martin J.
AU - Pedreño-Lopez, Núria
AU - Kwal, Jaclyn M.
AU - Ricciardi, Michael J.
AU - Myers, Tereance A.
AU - Julander, Justin G.
AU - Bohm, Rudolf P.
AU - Gilbert, Margaret H.
AU - Schiro, Faith
AU - Aye, Pyone P.
AU - Blair, Robert V.
AU - Martins, Mauricio A.
AU - Falkenstein, Kathrine P.
AU - Kaur, Amitinder
AU - Curry, Christine L.
AU - Kallas, Esper G.
AU - Desrosiers, Ronald C.
AU - Goldschmidt-Clermont, Pascal J.
AU - Whitehead, Stephen S.
AU - Andersen, Kristian G.
AU - Bonaldo, Myrna C.
AU - Lackner, Andrew A.
AU - Panganiban, Antonito T.
AU - Burton, Dennis R.
AU - Watkins, David I.
N1 - Funding Information:
This work was supported by the Bill and Melinda Gates Foundation (OPP1152818), the National Institutes of Health (NIH) grant 4P01AI094420-05, the Wallace H. Coulter Center for Translational Research at the University of Miami, the Miami Clinical and Translational Science Institute (CTSI), the Jacobson Jewish Community Foundation and Clarence Wolf Jr & Alma B Wolf Foundation, and the Intramural Research Program of the National Institute of Allergy and Infectious Diseases, NIH. This work was in part supported by NIH grant P51 OD011104 to the TNPRC, the NIH grant P30AI073961 to the Miami Center for AIDS Research, as well as the Defense Advanced Research Projects Agency (DARPA) Autonomous Diagnostics to Enable Prevention and Therapeutics: Prophylactic Options to Environmental and Contagious Threats (ADEPT-PROTECT) program (W31P4Q-13-1-0011). The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Publisher Copyright:
© 2018 The Author(s).
PY - 2018/12/1
Y1 - 2018/12/1
N2 - 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.
AB - 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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U2 - 10.1038/s41467-018-04056-4
DO - 10.1038/s41467-018-04056-4
M3 - Article
C2 - 29691387
AN - SCOPUS:85045999099
VL - 9
JO - Nature Communications
JF - Nature Communications
SN - 2041-1723
IS - 1
M1 - 1624
ER -