Performer: Public Health England (PHE)
Project leader: Miles W. Carroll, PhD
Initial contract value: $3.2 million
Contract modification value: $250,000 (March 2020)
Project dates: September 2015 - March 2021
In the course of responding to the 2014-2015 West African Ebola epidemic, regulatory authorities worldwide are working together to facilitate the rapid development and availability of medical countermeasures to detect, treat and prevent Ebola virus disease (EVD). In addition to policy and legal agreements and information sharing, these collaborations include regulatory science research.
Regulatory science helps FDA and other regulators learn if investigational medical products will help or harm patients, or have no effect. Scientists investigate these questions by developing tools, methods and standards to assess if these medical products are safe, and if they work.
Reference databases are an important part of regulatory science research because they provide standardized data that researchers can share and use to help develop new medical countermeasures. Regulators can use these databases to help assess safety and efficacy of these products.
Similarly, correlates of protection are measurable signs that a person is protected against a disease. For example, the presence of antibodies against a virus is often considered a correlate of protection.
In this Medical Countermeasures Initiative (MCMi) regulatory science project, Public Health England (PHE), will research issues that are key to understanding and predicting if—and how—vaccines and therapeutics to prevent and treat EVD will show efficacy.
PHE will establish correlates of protection to support potential licensure of new EVD vaccines, and analyze blood samples collected from patients with Ebola to create a reference database. The reference database will demonstrate biomarkers of disease progression in humans.
This project builds on previous studies by the European Mobile Laboratory (EMLab) and its associated research project (EVIDENT) in Guinea, Liberia and Sierra Leone, funded by the European Commission (EC).1 Collaborators include Laboratoire National de Santé Publique, Conakry, Guinea; Laboratoire des Fièvres Hémorragiques en Guineé, Université Gamal Abdel Nasser de Conakry, Guinea; the Bernhard-Nocht Institute for Tropical Medicine, Hamburg, Germany; The Phillips University of Marburg, Germany; and the University of Liverpool, Southampton and Bristol UK.
Sample collection and initial testing will be conducted at existing EMLab and EVIDENT facilities, and new facilities will be established in collaboration with Guinean partners in Conakry and Guéckédou, Guinea. High-resolution testing will be completed in the UK and Germany.
Image: Professor Miles Carroll arrives at an EVIDENT facility in Guinea with research equipment. (Credit: EVIDENT)
During this project, PHE, with University of Liverpool, will perform RNA sequencing analysis of up to 400 RNA samples from patients who became infected with EVD and survived or died during the 2014-2015 epidemic in West Africa.2 Deliverables include:
- Access to a cryopreserved biobank (under the ownership of the Guinean authorities) of up to 100 blood and plasma samples from volunteer Guinean Ebola survivors, from 1 month to 4 years after they have recovered from EVD. Up to four samples may be taken from each volunteer, at various time points.
- In-depth analysis of humoral and cellular response to naturally acquired immunity to EVD at various time periods including 1-14 months, and up to 2, 3 and 4 years post-infection.
- Reports comparing results from various tests on plasma from vaccinated volunteers and EVD survivors, to gauge differences in immunity between Ebola survivors and those who have received a vaccine.
Ultimately, this research will help identify a unique set of biomarkers of EVD, and expected disease outcomes. These tools will provide reference points for the development of new treatments and vaccines for Ebola, and help regulatory agencies evaluate the efficacy of urgently needed new medical products to treat and prevent EVD.
In March 2020, FDA modified this contract with PHE, including collaborators at the University of Liverpool (UoL) to apply technology used for the Ebola project to gather important information about COVID-19 infection. PHE and UoL are developing reagents and new methods to sequence the SARS-CoV-2 virus to create profiles of coronavirus for the rapid characterization of these viruses in humans and animal models. Ultimately, this study may support development and evaluation of medical countermeasures for COVID-19, including rapid diagnostics, therapeutics, and vaccines, and inform FDA evaluation of these products.
This project was funded through the MCMi Regulatory Science Extramural Research program
Carroll M, Matthews D, Hiscox J, et al. Temporal and spatial analysis of the 2014–2015 Ebola virus outbreak in West Africa. Nature. 2015 Aug 6;524:97-101. DOI: 10.1038/nature14594
Dowall S, Matthews D, Garcia-Dorival I, et al. Elucidating variations in the nucleotide sequence of Ebola virus associated with increasing pathogenicity. 2014 Nov 22;15(11):540. DOI: 10.1186/s13059-014-0540-x
2 Data will be compared to a control group of samples from United Kingdom residents with West African ancestry.
- Liu X, Speranza E, Muñoz-Fontela C, et al. Transcriptomic signatures differentiate survival from fatal outcomes in humans infected with Ebola virus. Genome Biol. 2017 Jan 17;18:4. DOI: 10.1186/s13059-016-1137-3 - full text (open access)
Also see related press release from the University of Liverpool
Shona C Moore, Rebekah Penrice-Randal, Muhannad Alruwaili, Xiaofeng Dong, Steven T Pullan, Daniel Carter, Kevin Bewley, Qin Zhao, Yani Sun, Catherine Hartley, En-min Zhou, Tom Solomon, Michael B. J. Beadsworth, James Cruise, Debby Bogaert, Derrick W T Crook, View ORCID ProfileDavid A Matthews, Andrew D. Davidson, Zana Mahmood, Waleed Aljabr, Julian Druce, Richard T Vipond, Lisa Ng, Laurent Renia, Peter Openshaw, View ORCID Profile J Kenneth Baillie, Miles W Carroll, Calum Semple, Lance Turtle, Julian Alexander Hiscox. Amplicon based MinION sequencing of SARS-CoV-2 and metagenomic characterisation of nasopharyngeal swabs from patients with COVID-19. MedRxiv; 2020 Mar 8. DOI: 10.1101/2020.03.05.20032011 - full text (open access)
Andrew D. Davidson, Maia Kavanagh Williamson, Sebastian Lewis, Deborah Shoemark, Miles W. Carroll, Kate Heesom, Maria Zambon, Joanna Ellis, Phillip A. Lewis, Julian A. Hiscox, View ORCID ProfileDavid A. Matthews. Characterisation of the transcriptome and proteome of SARS-CoV-2 using direct RNA sequencing and tandem mass spectrometry reveals evidence for a cell passage induced in-frame deletion in the spike glycoprotein that removes the furin-like cleavage site. BioRxiv. 2020 Mar 24. DOI: 10.1101/2020.03.22.002204 - full text (open access)
- Ebola Preparedness and Response Updates from FDA
- Supporting Field Laboratory Testing of Ebola Antibodies in Sierra Leone
- Decoding Ebola: Next-Generation Sequencing of the Ebola Genome for the FDA ARGOS Database
- Survivor Studies: Better Understanding Ebola's After-Effects to Help Find New Treatments
- EVIDENT project (EU)
- Coronavirus Disease 2019 (COVID-19)