In a Medical Countermeasures Initiative (MCMi) regulatory science project, Stanford University will analyze Ebola survivors with and without chronic health problems in an effort to identify factors responsible for driving prolonged disease well after the initial, acute infection.
This project will also explore immunopathology—how the immune system responds to diseases—and how it differs for various chronic post-Ebola signs and symptoms. This new data will provide valuable information to better understand the natural course of Ebola virus disease, and identify possible causes of chronic health problems in survivors.
The team will use a variety of approaches to analyze laboratory specimens, including CyTOF mass cytometry, and will make analysis readily interpretable by researchers around the world. Other analysis will include conducting Luminex cytokine and metabolomic assays (tests), evaluating clinical metrics, and creating multiplexed ion beam imaging (MIBI) 3D models of solid tissues, to better understand the relationships between tissue cells, immune cells and viral molecules.
The West African Ebola epidemic of 2014-2015 was the largest-ever Ebola outbreak, claiming more than 11,000 human lives. Unlike previous Ebola outbreaks, however, a large number of Ebola patients survived this epidemic.1 Many of the recent epidemic’s 16,000+ Ebola survivors suffer from chronic, long-term health problems including headaches, joint pain, and eye problems caused by Ebola.2 Scientists do not yet fully understand what causes these after-effects.
In September 2017, the U.S. Food and Drug Administration (FDA) modified this contract with Stanford University to apply the technology used for the Ebola project to gather critical information about the nature of Zika virus infection. The potential benefits of this additional study include improved understanding of congenital defects associated with maternal Zika virus infection and animal models of Zika virus infection.
In September 2019, FDA partnered with the National Institute of Allergy and Infectious Disease (NIAID), National Institutes of Health (NIH), to expand this project to apply a new method to the study of Ebola and Zika tissue samples. Under this project expansion, the Stanford laboratory will use multiplexed ion beam imaging (MIBI) to identify viral reservoirs—cells or anatomical sites where viruses accumulate and persist—for both Ebola and Zika infection.
In addition, the Stanford laboratory will explore the use of Quantum Barcoding (QBC)—an experimental diagnostic single-cell technology that can rapidly measure multiple targets including RNA, DNA, and proteins—to augment both mass cytometry and water-in-droplet based techniques as the primary means to analyze single cells in laboratory and field stations. At the end of this two-year collaboration, Stanford will deploy QBC to a federal laboratory facility at NIH for onsite testing and use in high-containment laboratories, including BSL-4 labs.
Ultimately, this research will help the global scientific community better understand the course of Ebola and Zika virus infections—an important factor in finding new treatments—and facilitate the deployment of novel, effective analytical technologies into federal laboratory space.
This project was funded through the MCMi Regulatory Science Extramural Research program.
