The EBO-PEP Project
Crédits photo : John Wessels/ALIMA
The Challenge of Protecting High-Risk Contacts Against Filovirus Disease (FVD)
Ebola, a persistent threat in sub-Saharan Africa
Since the devastating outbreak in West Africa between 2014 and 2016, Ebola virus disease (EVD)—one of the main filoviruses pathogenic to humans—has continued to emerge and re-emerge regularly in sub-Saharan Africa. In 2021, five years after the outbreak that caused more than 28,000 infections and more than 11,000 deaths in the region, Guinea faced a new outbreak. At the same time, the Democratic Republic of the Congo (DRC) periodically faces new Ebola outbreaks; the tenth outbreak (2018–2020) alone caused 3,470 infections and 2,287 deaths. Since then, the DRC has experienced six additional outbreaks. The most recent one, reported in early May 2026, is caused by the Bundibugyo virus and is also affecting neighboring Uganda. These repeated resurgences, with consistently very high case fatality rates, underscore the urgency of implementing more robust prevention and treatment strategies to protect the health of affected populations.
The existing therapeutic arsenal
Several tools have been developed to better combat the Ebola virus disease, including :
During the 2014–2016 West Africa epidemic, the rVSV-ZEBOV (Ervebo®) vaccine, developed by MSD-Merck, demonstrated its efficacy in the “Ebola ça suffit!” trial by reducing transmission and interrupting chains of infection.
It has since been widely used in ring vaccination strategies during recent outbreaks.
During the 10th outbreak in the RDC (2018–2020), the first randomized controlled trial evaluating four therapeutic agents for EVD treatment was conducted. Two monoclonal antibody therapies — REGN-EB3 (Inmazeb®) and MAb114 (Ebanga®) — demonstrated a significant reduction in mortality among patients diagnosed with EVD.
Monoclonal antibodies work by binding to specific proteins on the surface of the virus, preventing its entry into host cells. Additionally, they exert a direct antiviral action by neutralizing the virus and preventing its replication.
On March 15, 2024, a scientific article published in the journal Science confirmed the effectiveness ofa broad-spectrum antiviral,obeldesivir (GS-5245, a prodrug of remdesivir) developed by Gilead Sciences, in cynomolgus macaques infected with the Sudan virus (SUDV).
This treatment, which is administered orally and disrupts the virus’s replication cycle, has also shown partial efficacy against the Bundibugyo virus (BDBV).
Post-Exposure Prophylaxis (PEP) for high-risk contacts
In vaccinated individuals, there is a latency period between the time the vaccine is administered and the production of antibodies that provide protection. During this period, people who have had very close contact with an infected individual are potentially at risk of developing the disease. The EBO-PEP project aims to test a strategy designed to enhance protection for this group of high-risk contacts.
Several definitions of high-risk contacts for EVD have been proposed. The EBO-PEP project proposes a definition that considers both the clinical status of the “index case” (the infected patient) and the nature of the exposure, while remaining practical and easy to apply for field teams.
A high-risk contact in EBO-PEP is defined as:
- A person who has had direct contact with an individual with PCR-confirmed EVD presenting “wet symptoms” (diarrhea, vomiting, or external hemorrhage), or with their bodily fluids;
- A person who has had direct contact with the body of an individual with confirmed or probable EVD;
- A person who has sustained a needlestick injury from a syringe contaminated with the blood of a confirmed or probable EVD case;
- An infant born to or breastfed by an infected mother.
In addition to preventing disease in individuals, an effective PEP strategy could reduce the secondary attack rate, thereby interrupting transmission chains. If introduced quickly, this tool will not only curb the spread of the disease but also help combat filovirus epidemics.
The particular vulnerability of healthcare workers has been highlighted in multiple epidemics due to their close patient contact. An effective and accessible PEP could better protect this essential frontline workforce.
A Comprehensive Prevention Strategy for High-Risk Contacts
By incorporating PEP into their overall strategies for responding to epidemics, countries will be better able to control and mitigate the impact of filovirus epidemics on the health of their populations and their health care systems.
