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

doi:10.1038/s41467-018-04056-4

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. FalkensteinAmitinder 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

Research output: Contribution to journal › Article

20 Scopus citations

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 language	English (US)
Article number	1624
Journal	Nature communications
Volume	9
Issue number	1
DOIs	https://doi.org/10.1038/s41467-018-04056-4
State	Published - Dec 1 2018

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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., Gonzalez-Nieto, L., Gutman, M. J., Pedreño-Lopez, N., Kwal, J. M., Ricciardi, M. J., Myers, T. A., Julander, J. G., Bohm, R. P., Gilbert, M. H., Schiro, F., Aye, P. P., Blair, R. V., Martins, M. A., ... Watkins, D. I. (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 A.; Falkenstein, Kathrine P.; Kaur, Amitinder; Curry, Christine L.; Kallas, Esper G.; Desrosiers, Ronald C.; Goldschmidt-Clermont, Pascal J.; Whitehead, Stephen S.; Andersen, Kristian G.; Bonaldo, Myrna C.; Lackner, Andrew A.; Panganiban, Antonito T.; Burton, Dennis R.; Watkins, David I.

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

Research output: Contribution to journal › Article

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, MA, Falkenstein, KP, Kaur, A, Curry, CL, Kallas, EG, Desrosiers, RC, Goldschmidt-Clermont, PJ, Whitehead, SS, Andersen, KG, Bonaldo, MC, Lackner, AA, Panganiban, AT, Burton, DR & Watkins, DI 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, 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 A. ; Falkenstein, Kathrine P. ; Kaur, Amitinder ; Curry, Christine L. ; Kallas, Esper G. ; Desrosiers, Ronald C. ; Goldschmidt-Clermont, Pascal J. ; Whitehead, Stephen S. ; Andersen, Kristian G. ; Bonaldo, Myrna C. ; Lackner, Andrew A. ; Panganiban, Antonito T. ; Burton, Dennis R. ; Watkins, David I. / 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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10.1038/s41467-018-04056-4