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 Martins, Kathrine P. FalkensteinAmitinder Kaur, Christine Curry, Esper G. Kallas, Ronald Charles Desrosiers, Pascal Goldschmidt-Clermont, Stephen S. Whitehead, Kristian G. Andersen, Myrna C. Bonaldo, Andrew A. Lackner, Antonito T. Panganiban, Dennis R. Burton, David Watkins

Research output: Contribution to journalArticle

17 Citations (Scopus)

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.

Original languageEnglish (US)
Article number1624
JournalNature Communications
Volume9
Issue number1
DOIs
StatePublished - Dec 1 2018

Fingerprint

Fetal Death
Macaca
viruses
infectious diseases
antibodies
Viruses
therapy
Antibodies
Viremia
Amniotic Fluid
Fetal Development
Macaca mulatta
Therapeutics
Monoclonal Antibodies
Mothers
Primates
Haplorhini
Brazil
Zika Virus
Zika Virus Infection

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this

Magnani, D. M., Rogers, T. F., Maness, N. J., Grubaugh, N. D., Beutler, N., Bailey, V. K., ... Watkins, D. (2018). Fetal demise and failed antibody therapy during Zika virus infection of pregnant macaques. Nature Communications, 9(1), [1624]. https://doi.org/10.1038/s41467-018-04056-4

Fetal demise and failed antibody therapy during Zika virus infection of pregnant macaques. / Magnani, Diogo M.; Rogers, Thomas F.; Maness, Nicholas J.; Grubaugh, Nathan D.; Beutler, Nathan; Bailey, Varian K.; Gonzalez-Nieto, Lucas; Gutman, Martin J.; Pedreño-Lopez, Núria; Kwal, Jaclyn M.; Ricciardi, Michael J.; Myers, Tereance A.; Julander, Justin G.; Bohm, Rudolf P.; Gilbert, Margaret H.; Schiro, Faith; Aye, Pyone P.; Blair, Robert V.; Martins, Mauricio; Falkenstein, Kathrine P.; Kaur, Amitinder; Curry, Christine; Kallas, Esper G.; Desrosiers, Ronald Charles; Goldschmidt-Clermont, Pascal; Whitehead, Stephen S.; Andersen, Kristian G.; Bonaldo, Myrna C.; Lackner, Andrew A.; Panganiban, Antonito T.; Burton, Dennis R.; Watkins, David.

In: Nature Communications, Vol. 9, No. 1, 1624, 01.12.2018.

Research output: Contribution to journalArticle

Magnani, DM, Rogers, TF, Maness, NJ, Grubaugh, ND, Beutler, N, Bailey, VK, Gonzalez-Nieto, L, Gutman, MJ, Pedreño-Lopez, N, Kwal, JM, Ricciardi, MJ, Myers, TA, Julander, JG, Bohm, RP, Gilbert, MH, Schiro, F, Aye, PP, Blair, RV, Martins, M, Falkenstein, KP, Kaur, A, Curry, C, Kallas, EG, Desrosiers, RC, Goldschmidt-Clermont, P, Whitehead, SS, Andersen, KG, Bonaldo, MC, Lackner, AA, Panganiban, AT, Burton, DR & Watkins, D 2018, 'Fetal demise and failed antibody therapy during Zika virus infection of pregnant macaques', Nature Communications, vol. 9, no. 1, 1624. https://doi.org/10.1038/s41467-018-04056-4
Magnani DM, Rogers TF, Maness NJ, Grubaugh ND, Beutler N, Bailey VK et al. Fetal demise and failed antibody therapy during Zika virus infection of pregnant macaques. Nature Communications. 2018 Dec 1;9(1). 1624. https://doi.org/10.1038/s41467-018-04056-4
Magnani, Diogo M. ; Rogers, Thomas F. ; Maness, Nicholas J. ; Grubaugh, Nathan D. ; Beutler, Nathan ; Bailey, Varian K. ; Gonzalez-Nieto, Lucas ; Gutman, Martin J. ; Pedreño-Lopez, Núria ; Kwal, Jaclyn M. ; Ricciardi, Michael J. ; Myers, Tereance A. ; Julander, Justin G. ; Bohm, Rudolf P. ; Gilbert, Margaret H. ; Schiro, Faith ; Aye, Pyone P. ; Blair, Robert V. ; Martins, Mauricio ; Falkenstein, Kathrine P. ; Kaur, Amitinder ; Curry, Christine ; Kallas, Esper G. ; Desrosiers, Ronald Charles ; Goldschmidt-Clermont, Pascal ; Whitehead, Stephen S. ; Andersen, Kristian G. ; Bonaldo, Myrna C. ; Lackner, Andrew A. ; Panganiban, Antonito T. ; Burton, Dennis R. ; Watkins, David. / Fetal demise and failed antibody therapy during Zika virus infection of pregnant macaques. In: Nature Communications. 2018 ; Vol. 9, No. 1.
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