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 › peer-review

34 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

ASJC Scopus subject areas

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

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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 › peer-review

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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title = "Fetal demise and failed antibody therapy during Zika virus infection of pregnant macaques",

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.",

author = "Magnani, {Diogo M.} and Rogers, {Thomas F.} and Maness, {Nicholas J.} and Grubaugh, {Nathan D.} and Nathan Beutler and Bailey, {Varian K.} and Lucas Gonzalez-Nieto and Gutman, {Martin J.} and N{\'u}ria Pedre{\~n}o-Lopez and Kwal, {Jaclyn M.} and Ricciardi, {Michael J.} and Myers, {Tereance A.} and Julander, {Justin G.} and Bohm, {Rudolf P.} and Gilbert, {Margaret H.} and Faith Schiro and Aye, {Pyone P.} and Blair, {Robert V.} and Martins, {Mauricio A.} and Falkenstein, {Kathrine P.} and Amitinder Kaur and Curry, {Christine L.} and Kallas, {Esper G.} and Desrosiers, {Ronald C.} and Goldschmidt-Clermont, {Pascal J.} and Whitehead, {Stephen S.} and Andersen, {Kristian G.} and Bonaldo, {Myrna C.} and Lackner, {Andrew A.} and Panganiban, {Antonito T.} and Burton, {Dennis R.} and Watkins, {David I.}",

note = "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.",

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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.

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.

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