Study Overview 
Investigator: O'Connor and Osorio Grant: NIH P51 to WNPRC and NIH R01 supplement 3R01AI116382-01A1S1 to O'Connor


ZIKV-026 tracks data in 34 datasets over 514 time points. Data is present for 2 Participants.

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ZIKV-026: Dose titration of ZIKV in pregnant macaques 

Primary objectives

We will test the hypothesis that the risk of fetal injury due to Zika virus infection is proportional to the amount of virus present. This question is of great importance to the field as a whole, if this hypothesis is correct we hope to provide the basis for a model of microcephaly by establishing a dose of Zika virus that is likely to result in microcephaly. We will follow fetal development closely, looking for signs of microcephaly or fetal injury similar to microcephaly.

Study design

Two pregnant Indian-origin rhesus macaques will be infected with a high dose of ZIKV Puerto Rico (PRVABC59) around gestational day 45. The animals will be inoculated with 5 subcutaneous doses of 10e7 PFU of virus. Plasma, urine and saliva viral loads will be measured frequently immediately following infection, then biweekly for the duration of positive plasma viremia, and then weekly throughout pregnancy. The fetus will be monitored by weekly by ultrasound.

Participants

Clinical and Assay Data

Viral RNA Quantification

Clinical

Updates

May 2, 2017: Participant 125500 was challenged with five subcutaneous doses of 10e7 PFU of ZIKV Puerto Rico (three injections into the left forearm and two in the right) at 50 days of gestation.
  • Peak viral load was reached at 2 DPI with a plasma viral load of 6.6e7.
  • Plasma viremia was resolved by 24 DPI, with the last positive plasma viral at 21 DPI.
  • Currently, the fetus is scheduled to be delivered via c-section August 15, 2016.
  • August 15, 2017: Fetus 411377 was scheduled to be delivered by C-section today. The fetus was stillborn. Gross analysis suggests intrauterine death within the last few days. The fetus appeared normal at delivery and ultrasound was unremarkable when performed 7 days ago. This is the second instance of fetal death we have observed following maternal infection with PRVABC59, the other was described here
  • On the day of the C-section bacterial cultures were taken from the following fetal and maternal-fetal interface sites: lung, liver, spleen, stomach, umbilicus tissue, amniotic fluid, placenta, and uterine tissue. All bacterial cultures were negative.
  • Ocular histology for the still born fetus 411377 results came back with no defects noted beyond the expected moderate to severe autolysis. The full pathology report can be read here.

  Attached Files  
   
 Bacterial_cultures.pdf
 ZIKV-026_fetus_ocular_histology.pdf


Plasma viral load 

Pan urine viral load 

Oral swab viral load 

Necropsy Tissue Viral Load 

Necropsy tissue viral load: maternal and fetal maternal interface 
FilterGrid ViewsReportsChartsGroupsExportPrintPagingView Specimens
Participant ID
Date
Tissue
vRNA copies / mg
 1255002017-08-15amniotic/chorionic membrane27.647
1255002017-08-15decidua26.1595
1255002017-08-15liver8.4337
1255002017-08-15mesenteric LN0.0
1255002017-08-15placental disc 18.9611
1255002017-08-15placental disc 20.0
1255002017-08-15spleen0.0
1255002017-08-15uterus - placental bed112.3878

Necropsy tissue viral loads: fetal 
FilterGrid ViewsReportsChartsGroupsExportPrintPagingView Specimens
Participant ID
Date
Tissue
vRNA copies / mg
 4113772017-08-15axillary LN15.6451
4113772017-08-15cerebrum 10 right28.0876
4113772017-08-15 cerebrum 1 right35.7651
4113772017-08-15 cerebrum 2 right55.1085
4113772017-08-15cerebrum 4 right55.7062
4113772017-08-15cerebrum 7 right32.344
4113772017-08-15cervical spinal cord33.6162
4113772017-08-15colon0.0
4113772017-08-15cornea631.9209
4113772017-08-15dura Mater28.8981
4113772017-08-15epidermis/dermis abdomen31.3233
4113772017-08-15eye-optic nerve322.2222
4113772017-08-15heart 19.4178
4113772017-08-15inguinal LN0.0
4113772017-08-15kidney 60.5981
4113772017-08-15lumbar spinal cord54.677
4113772017-08-15lung23.1326
4113772017-08-15mesenteric LN201.0135
4113772017-08-15ovary632.2857
4113772017-08-15pituitary gland0.0
4113772017-08-15retina695.9183
4113772017-08-15sclera73.4018
4113772017-08-15spleen86.7924
4113772017-08-15stomach36.8055
4113772017-08-15submandibular LN118.3098
4113772017-08-15thoracic spinal cord54.6315
4113772017-08-15thymus15.6193
4113772017-08-15tonsil 750.0
4113772017-08-15tracheobroncial LN0.0
4113772017-08-15urinary bladder18.1297
4113772017-08-15uterus126.3888