1. Fetal demise and failed antibody therapy during Zika virus infection of pregnant macaques.
- Author
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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, and Watkins DI
- Subjects
- Animals, Antibodies, Neutralizing administration & dosage, Female, Fetal Death, Humans, Macaca mulatta, Pregnancy, Pregnancy Complications mortality, Pregnancy Complications virology, Zika Virus drug effects, Zika Virus genetics, Zika Virus Infection mortality, Zika Virus Infection virology, Antibodies, Viral administration & dosage, Pregnancy Complications drug therapy, Zika Virus physiology, Zika Virus Infection drug therapy
- 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.
- Published
- 2018
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