The EBO-PEP Project

Crédits photo : John Wessels/ALIMA

The challenge of protecting high-risk contacts against MVE

Ebola, a persistent threat in sub-Saharan Africa

Since the devastating outbreak in West Africa between 2014 and 2016, Ebola Virus Disease (EVD) has continued to emerge and re-emerge across Sub-Saharan Africa. In 2021, five years after an epidemic that caused over 28,000 infections and more than 11,000 deaths, Guinea faced another outbreak. At the same time, the Democratic Republic of the Congo (RDC) has continued to experience recurrent Ebola epidemics. The 10th outbreak (2018–2020) alone resulted in 3,470 infections and 2,287 deaths. Since then, the country has experienced five additional outbreaks, the most recent officially declared in September 2025. These repeated resurgences, with consistently high mortality rates, highlight the urgent need for more robust prevention and treatment strategies to protect affected populations.

The current therapeutic arsenal against EVD

Several tools have been developed to better combat the Ebola virus disease, including :

vaccin
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.
no-virus

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.

Despite these advances, high mortality rates in recent outbreaks in the RDC (around 50%) reveal persistent gaps in current strategies — particularly for high-risk contacts who require immediate and reliable protection.


Post-Exposure Prophylaxis (PEP) for high-risk contacts

Among vaccinated individuals, there is a delay between vaccination and the development of protective antibodies. During this window period, individuals with close, high-risk exposure may still develop the disease. The EBO-PEP project aims to test a strategy designed to reinforce 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.

Beyond preventing disease in exposed individuals, an effective PEP strategy could reduce the secondary attack rate, helping break chains of transmission. If introduced quickly, this tool will not only help to halt the spread of the disease, but also contribute to the fight against MVE 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: combining PEP and vaccination

To effectively control EVD outbreaks, a complete prevention approach for high-risk contacts is necessary. The EBO-PEP strategy proposes combining:

  • Immediate, short-term protection using monoclonal antibodies to prevent progression to EVD;
  • Long-term protection through vaccination to ensure lasting immunity.

By integrating PEP into national outbreak response plans, countries will be better equipped to control transmission, reduce epidemic impact, and protect both populations and health systems.