The EBO-PEP Project: a new strategy to prevent filovirus disease among high-risk contacts

The Ebola virus disease (EVD) remains one of the most feared filovirus infections in the world. Characterised by rapid transmission and high mortality, it poses a major challenge to health systems, particularly during outbreaks.

Strains of the Ebola virus (EBOV) that are pathogenic to humans are transmitted through direct contact with an infected person, their bodily fluids — such as blood, saliva, urine, faeces or breast milk — or with the body of someone who has died from the disease. Due to its dangerous nature, EBOV, like all filoviruses, is classified as a biosafety level 4 agent.

Since its identification in 1976 in the Democratic Republic of the Congo, several epidemics have been recorded. To date, the largest Ebola virus disease (EVD) outbreak occurred in West Africa between 2014 and 2016. It resulted in more than 28,000 infections and more than 11,000 deaths (a mortality rate of 40 per cent).¹ This health crisis highlighted a crucial reality: to control Ebola, it is not enough simply to treat those who are ill — it is also necessary to protect those who have been exposed as quickly as possible.

Protection after exposure: the principle of post-exposure prophylaxis

The post-exposure prophylaxis (PEP) strategy in the EBO-PEP trial is defined as the treatment of individuals at high risk of filovirus disease (FVD). The main aim of PEP is to prevent the development of FVD following exposure to the virus.

In the case of Ebola, this approach targets people who have had high-risk contact with an infected patient. The aim is twofold:

• to prevent the development of the disease in exposed individuals;
• to break the chains of transmission by reducing secondary infections.

Previous outbreaks have shown that certain populations are particularly vulnerable, notably healthcare workers and patients’ close contacts. Having a rapid and effective protection strategy is therefore a key factor in safeguarding the public health response and limiting the scale of outbreaks.

Methodology of the EBO-PEP trial: an innovative approach to prevention

EBO-PEP (ANRS 0515s) is a randomised, controlled platform trial. It aims to evaluate different post-exposure prophylaxis strategies among FVD contacts during a specific outbreak. Treatment comparisons may utilise flexible methodologies and are described in sub-protocols appended to a master protocol. Each sub-protocol is named according to the investigational medicinal product (IMP) concerned and the target viral species.

Participants are individually randomised into different intervention arms depending on the virus and the options available for post-exposure prophylaxis (PEP) during a specific outbreak. The total duration of follow-up for trial participants is 42 days or until the end of hospitalisation at an Ebola Treatment Centre (ETC) for confirmed cases of filovirus disease. All participants are monitored daily for at least 21 days.

Two investigational drugs against the Bundibugyo virus

The initial phase of the EBO-PEP trial aims, through a first sub-protocol, to assess the safety and efficacy of obeldesivir—an antiviral developed by Gilead Sciences—as PEP in individuals aged over 12 years at high risk of infection with the Bundibugyo Ebola virus in the DRC and Uganda.

A second sub-protocol, conducted in parallel, aims to assess the efficacy of another antiviral, remdesivir, against the same virus in children under 12 and in pregnant or breastfeeding women. This is because the available data on obeldesivir in these specific populations are insufficient to support its use.

Who is considered to be at high risk?

The study involves people who have been exposed in situations where transmission of the virus is particularly likely. Contact is considered high-risk when it involves, in particular²:

• Direct contact with a person with a confirmed FVD, presenting with diarrhea, vomiting or external haemorrhages (‘wet symptoms’), or with their bodily fluids;
• Direct contact with the dead body of a person with FVD;
• A needle injection with a syringe contaminated with the blood of a person with confirmed or probable FVD;
• or a child born to or breastfed by a person with FVD

Know more about EBO-PEP’s protocol

Consortium members

• National Health Security Agency (ANSS)
• The Alliance for International Medical Action (ALIMA)
• ANRS Emerging Infectious Diseases (ANRS MIE)
• PAC–CI Association (PAC–CI)
• Barcelona Institute for Global Health (ISGLOBAL)
• National Institute for Biomedical Research (INRB)
• National Institute of Health and Medical Research (Inserm)
• National Institute of Public Health (INSP)
• Médecins Sans Frontières (MSF)
• Pandemic Preparedness Platform for Health and Emerging Infections Response (PANTHER)
• University of Bordeaux (UB)
• Gamal Abdel Nasser University, Conakry (CERFIG)
• Mbarara University of Science and Technology (MUST)
• Cheikh Anta Diop University of Dakar (UCAD)

Funding bodies

This project 101145675 – EBO-PEP – HORIZON-JU-GHEDCTP3-2023-01 is supported by the European Union’s Global Health EDCTP3 partnership.

References

1. WHO | Regional Office for Africa [Internet]. Ebola Disease. Disponible sur: https://www.afro.who.int/health-topics/ebola-disease. (accédé le 20/03/2026)
2. Hoffmann Dahl E, Mbala P, Juchet S, Touré A, Montoyo A, Serra B, et al. Improving Ebola virus disease outbreak control through targeted post-exposure prophylaxis. Lancet Glob Health. 2024;12(10):e1730‑6