Project leader: Maria Rosa Capobianchi, PhD, in collaboration with Gerardo Kaplan, PhD, FDA Center for Biologics Evaluation and Research (CBER)
Contract value: $310,0001
Project dates: September 2015 - September 2018
Image: Isolation glove box in the INMI Goderich Lab, Freetown, Sierra Leone (Credit: INMI)
As part of FDA’s response to the 2014-2015 West African Ebola epidemic, the agency has funded several regulatory science research projects to further the rapid development and availability of medical countermeasures (MCMs) to diagnose, treat and prevent Ebola virus disease (EVD). This research includes both intramural and extramural projects, and in some cases, a combination of the two.
With funding from the Medical Countermeasures Initiative (MCMi), FDA’s Office of Blood Research and Review (OBRR) in the Center for Biologics Evaluation and Research (CBER) has developed antibody tests to evaluate the protective immunity of investigational Ebola vaccines. Under the direction of Dr. Gerardo Kaplan, FDA developed antibody assays (tests) that could be deployed in West African laboratories to analyze clinical trial samples.
Clinical trials to evaluate potential Ebola vaccines and therapeutics are underway in West Africa, but the ability to perform tests to evaluate if these products work is currently limited, as samples of blood and fluids from Ebola patients usually require the highest levels of biocontainment, biosafety level 4 (BSL-4). There are currently no BSL-4 lab capabilities in West Africa, and transporting the samples overseas for testing is complicated and expensive.
In this MCMi regulatory science project, the National Institute for Infectious Diseases “Lazzaro Spallanzani” (INMI) in Rome, Italy, will work with Dr. Kaplan’s FDA lab to perform field validation of the FDA-developed antibody tests, which can be conducted at the less-restrictive biosafety level 2. Field laboratories in West Africa currently do not have this testing capability.
INMI will establish field capability to analyze anti-Ebola virus glycoprotein antibodies in the INMI Goderich Lab in Freetown, Sierra Leone.2 They will adapt the FDA-developed tests to work with the available field equipment and conditions. For example, field tests may use an antibody that is stable at room temperature, rather than one that requires refrigeration.
Image: Research area addressed: facilitate development of MCMs to protect against threats to U.S. and global health security. Image of gears with text: seroprevalence studies, optimizing collection of convalescent plasma, EBOV BSL-2 ELISA and PRNT neutralization tests, tech transfer for long-term sustainability, kinetics of Ab response. (Credit: INMI)
During this two-year project, INMI will work with FDA to:
- Deploy Ebola virus glycoprotein BSL-2 total and neutralizing antibody assays in Sierra Leone,
- Validate the antibody assays using clinical samples from the Emergency Treatment Center (ETC) in Goderich, Sierra Leone, and
- Perform a seroprevalence study using samples from asymptomatic volunteers (i.e., volunteers who are not reporting symptoms of Ebola infection) in Sierra Leone. These seroprevalence tests will measure the frequency of Ebola- specific antibodies in blood serum, providing indirect information on the frequency of asymptomatic infections.
This new capability to evaluate samples in field labs will be instrumental in expanding other Ebola MCM evaluation activities in West Africa. In addition, this project will help the global public health and scientific community better understand the biology and epidemiology of the Ebola virus—an important part of supporting evaluation of current and future clinical trial data for vaccines, serum therapies (such as monoclonal antibodies and convalescent plasma), and other Ebola MCMs.
This project was funded through the MCMi Regulatory Science Extramural Research program, and builds on work funded through the MCMi Regulatory Science Intramural Research program.
Capobianchi MR, Gruber CE, Carletti F, Meschi S, Castilletti C, Vairo F, Biava M, Minosse C, Strada G, Portella G, Miccio R, Minardi V, Rolla L, Kamara A, Chillemi G, Desideri A, Di Caro A, Ippolito G. Molecular Signature of the Ebola Virus Associated with the Fishermen Community Outbreak in Aberdeen, Sierra Leone, in February 2015. Genome Announc. 2015 Sep 24;3(5). pii: e01093-15. DOI: 10.1128/genomeA.01093-15.
Castilletti C, Carletti F, Gruber CE, Bordi L, Lalle E, Quartu S, Meschi S, Lapa D, Colavita F, Chiappini R, Mazzarelli A, Marsella P, Petrosillo N, Nicastri E, Chillemi G, Valentini A, Desideri A, Di Caro A, Ippolito G, Capobianchi MR. Molecular Characterization of the First Ebola Virus Isolated in Italy, from a Health Care Worker Repatriated from Sierra Leone. Genome Announc. 2015 Jun 18;3(3). pii: e00639-15. DOI: 10.1128/genomeA.00639-15.
Ippolito G, Lanini S, Brouqui P, Di Caro A, Vairo F, Abdulla S, Fusco FM, Krishna S, Capobianchi MR, Kyobe-Bosa H, Lewis DJ, Puro V, Wolfel R, Avsic-Zupanc T, Dar O, Mwaba P, Bates M, Heymann D, Zumla A. Ebola: missed opportunities for Europe-Africa research. Lancet Infect Dis. 2015 Jul 28. pii: S1473-3099(15)00236-4. DOI: 10.1016/S1473-3099(15)00236-4.
Konduru K, Shurtleff A, Bavari S, Kaplan G. Evaluation of ebolavirus glycoprotein Fc fusion protein as a subunit vaccine (P4417). J Immunol. 2013 May;190:205.18. DOI
Lanini S, Portella G, Vairo F, Kobinger GP, Pesenti A, Langer M, Kabia S, Brogiato G, Amone J, Castilletti C, Miccio R, Zumla A, Capobianchi MR, Di Caro A, Strada G, Ippolito G, and INMI-EMERGENCY EBOV Sierra Leone Study group. Blood kinetics of Ebola virus in survivors and nonsurvivors. J Clin Invest. 2015;125(12):4692-4698. DOI:10.1172/JCI83111.
Petrosillo N, Nicastri E, Lanini S, Capobianchi MR, Di Caro A, Antonini M, Puro V, Lauria FN, Shindo N, Magrini N, Kobinger GP, Ippolito G; INMI EBOV Team. Ebola virus disease complicated with viral interstitial pneumonia: a case report. BMC Infect Dis. 2015 Oct 16;15(1):432. DOI: 10.1186/s12879-015-1169-4.
1 This amount is the total contract value of the extramural research BAA award to INMI. The intramural research challenge grant to Dr. Kaplan at FDA was funded for an additional $35,000 in May 2015.
2 The INMI Lab in Goderich was built by the British Army (UK Ministry of Defence), financed by the UK Department of International Development (DFID), and operated by the Italian non-government organization (NGO) EMERGENCY. The Ebola Treatment Unit (ETU) at this site stopped treating patients in May 2015, but the facility is now in use as a research laboratory to support development of Ebola vaccines and treatments. Learn more about the facility at: http://www.emergency.it/sierraleone/ebola-treatment-unit-goderich.html
FDA Science Forum 2017 Presentation
- Development of Total and Neutralizing Anti-Ebola Virus Antibody Assays for Deployment in West Africa to Evaluate Clinical Trials of MCM, including Vaccines and Immunotherapies
June 1, 2017 presentation at the 2017 FDA Science Forum by Geraldo Kaplan, PhD, Principal Investigator, CBER (recording at 1:11:20-1:28:50)
- Ebola Preparedness and Response Updates from FDA
- Decoding Ebola: Next-Generation Sequencing of the Ebola Genome for the FDA ARGOS Database
- Developing a Toolkit to Assess Efficacy of Ebola Vaccines and Therapeutics
- Survivor Studies: Better Understanding Ebola's After-Effects to Help Find New Treatments