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


ZIKV-023 tracks data in 34 datasets over 513 time points. Data is present for 4 Participants.

Study Navigator
Study Navigator

ZIKV-023 

Primary objectives

We will examine and compare acute infection dynamics (14 days) with the ZIKV strain PRVABC59 between four Indian rhesus macaques infected via mosquito bite (Aedes aegypti, black-eyed Liverpool strain) and animals we previously infected with ZIKV strain PRVABC59 by subcutaneous inoculation (ZIKV-022). Animals will be euthanized after 14 dpi and 20+ tissues will be collected and processed for RNA isolation and viral load. These experiments will examine whether subcutaneous inoculation accurately represents mosquito infection in rhesus macaques and whether infection by mosquito bite results in increased plasma viral loads and more extensive tissue burden similar to that observed for other flaviviruses such as West Nile virus.

The total number of blood fed mosquitoes per animal and the amount of infectious ZIKV in the saliva of those mosquitoes will be used to estimate the dose of inoculum each animal receives. Blood fed mosquitoes will be examined for infection (detection of ZIKV in the midgut), dissemination (detection of ZIKV in the extremities), and transmission by capillary feeding (detection of ZIKV in the saliva).

Study design

Four Indian-origin rhesus macaques (3 males, 1 female) will be infected by mosquito bite with ZIKV Puerto Rico (PRVABC59). Blood plasma, urine, and saliva will be collected from each animal at -4, and 0-14 dpi, and serum will be collect at 0 and 14 dpi. Viral RNA will be measured using qRT-PCR for all sample types and will be compared between these animals and animals infected subcutaneously with 104 PFU WT PRVABC59 in a previous study (ZIKV-022). In addition, we will be collecting tissues from these animals at necropsy including lymph nodes, CNS tissues, and reproductive tissues.

Participants

  • 268283 will be challenged by mosquito feeding
  • 328696 will be challenged by mosquito feeding
  • 349332 will be challenged by mosquito feeding
  • 458001 will be challenged by mosquito feeding

Clinical and Assay Data

Viral RNA quantification

Clinical

Updates

  • January 30, 2017: This study is scheduled to begin on January 30, 2017. All animals were successfully fed on by mosquitoes on January 30, 2017; 328696 received 18 bites, 349332 received 8 bites, 268283 received 5 bites, 458001 received 5 bites.
  • January 31, 2017: As of 1 day post challenge, 328696, 349332, and 458001 all had positive plasma viral loads.
  • February 2, 2017: 268283 finally had a positive plasma viral load 2 days post challenge.


Visual Study Design 

Visual Study Design

  Attached Files  
   
 Mosquito_visual_study_design.jpg


Plasma viral load 

Pan urine viral load 

CSF viral load 

Mosquito data 

328696 received 18 bites
349332 received 8 bites
268283 received 5 bites
458001 received 5 bites

A Mosquito bite is defined as a mosquito ingesting blood.

 

Figure showing the percent of infection, dissemination, and transmission of ZIKV in the 40 mosquitoes that fed on the animals. 

Scatter plot of the saliva ZIKV titer from the mosquitoes that feed on the Group 1 and Group 2 animals. 

Mosquito viral loads
Viral loads from ZIKV-positive mosquitoes that fed on the animals.

  Attached Files  
   
 mosquito_viral_load.jpg
 ZIKV-023_saliva_scatter.jpg
 ZIKV-023_mosquito_data.jpg


Necropsy tissue viral load 
FilterGrid ViewsReportsChartsGroupsExportPrintPagingView Specimens
Participant ID
Date
Tissue
vRNA copies / mg
 2682832017-02-16axillary LN5058.8
4580012017-02-15axillary LN1387.0
3286962017-02-16axillary LN3643.7
3493322017-02-15axillary LN1912.28
4580012017-02-15bone marrow1.91
3286962017-02-16bone marrow2.96
3493322017-02-15bone marrow8.41
2682832017-02-16bone marrow0.0
4580012017-02-15cerebrum0.0
2682832017-02-16cerebrum0.0
3493322017-02-15cerebrum0.0
3286962017-02-16cerebrum0.0
3493322017-02-15cerebrum: frontal lobe0.0
4580012017-02-15cerebrum: frontal lobe0.0
2682832017-02-16cerebrum: hippocampus0.0
4580012017-02-15cerebrum: hippocampus0.0
3493322017-02-15cerebrum: hippocampus0.0
3286962017-02-16cerebrum: hippocampus0.0
4580012017-02-15cervix29.8
2682832017-02-16eye-aqueous humor0.0
3286962017-02-16eye-aqueous humor0.0
3493322017-02-15eye-aqueous humor0.0
4580012017-02-15eye-aqueous humor0.0
2682832017-02-16eye lid conjunctiva0.0
4580012017-02-15eye lid conjunctiva0.0
3493322017-02-15eye lid conjunctiva0.0
3286962017-02-16eye-lid conjunctiva0.0
3286962017-02-16eye-optic nerve0.0
4580012017-02-15eye-optic nerve0.0
3493322017-02-15eye-optic nerve0.0
2682832017-02-16eye-optic nerve0.0
3286962017-02-16eye-sclera retina0.0
2682832017-02-16eye-sclera retina0.0
4580012017-02-15eye-sclera retina0.0
3493322017-02-15eye-sclera retina0.0
2682832017-02-16inguinal LN0.0
3286962017-02-16inguinal LN3554.3
4580012017-02-15inguinal LN5285.7
3493322017-02-15kidney0.0
4580012017-02-15kidney377.09
2682832017-02-16kidney0.0
3286962017-02-16kidney3238.81
3493322017-02-15liver35.0
4580012017-02-15liver65.25
3286962017-02-16liver23.86
2682832017-02-16liver12.17
2682832017-02-16lung0.0
3286962017-02-16lung0.0
4580012017-02-15lung0.0
3493322017-02-15lung0.0
3286962017-02-16mesenteric LN89677.4
2682832017-02-16mesenteric LN5976.7
4580012017-02-15mesenteric LN181111.11
3493322017-02-15mesenteric LN6226.01
4580012017-02-15ovarian follicle0.0
4580012017-02-15ovary0.0
4580012017-02-15pelvic LN2915.3
3493322017-02-15pelvic LN1334.44
3286962017-02-16pelvic LN2966.8
2682832017-02-16pelvic LN2576.5
2682832017-02-16prostate0.0
3493322017-02-15prostate0.0
3286962017-02-16prostate0.0
3286962017-02-16seminal vesicle0.0
3493322017-02-15seminal vesicle0.0
2682832017-02-16seminal vessicle0.0
3493322017-02-15spleen3931.5
2682832017-02-16spleen3211.9
4580012017-02-15spleen0.0
3286962017-02-16spleen2941.6
4580012017-02-15submandibular LN391.7
3286962017-02-16submandibular LN488.3
2682832017-02-16submandibular LN311.0
3493322017-02-15submandibular LN334.3
3493322017-02-15testicle0.0
3286962017-02-16testicle0.0
2682832017-02-16testicle0.0
3286962017-02-16tracheobronchial LN0.0
3493322017-02-15tracheobronchial LN318.25
4580012017-02-15tracheobronchial LN0.0
2682832017-02-16tracheobronchial LN0.0
4580012017-02-15uterus0.0
4580012017-02-15vagina44.4

Necropsy Tissue Viral Load