EBO-PEP

The challenge

Ebola virus infections arise periodically in multiple sub-Saharan African countries. Outbreaks are associated with very high mortality, with the close contacts of infected patients being the most at risk.

Vaccines have been developed for the most common Ebola virus infection, Zaire ebolavirus, and the r-VSV-ZEBOV vaccine is now widely used in ‘ring vaccination’ strategies to contain outbreaks. However, vaccination does not generate immediate protection, leaving those who have already been exposed to infected patients at high risk of infection and disease.

Monoclonal antibodies, which can block infection of cells by Ebola viruses, offer a complementary prevention strategy. Because they provide immediate projection, they could be of particular value to close contacts of patients. Two monoclonal antibodies, ansuvimab and REGN-EB3, have been approved by the US Food and Drug Administration (FDA) for the prevention of Zaire ebolavirus infection. 

Monoclonal antibodies have been used in the Democratic Republic of the Congo (DRC) through an emergency use protocol, and no infections occurred in people receiving such post-exposure prophylaxis (PEP). However, these products have not yet been rigorously evaluated in a clinical trial.

The project

The EBO-PEP project is designed to provide reliable data on the efficacy of monoclonal antibody PEP for Zaire ebolavirus. Evaluating preventive interventions for Ebola virus outbreaks is challenging, due to their sporadic nature, the need for a rapid response, and their short duration (if they are controlled effectively).

To address these challenges, the EBO-PEP project is establishing an infrastructure that will enable rapid trial launches in response to outbreaks and facilitate the pooling of data from multiple outbreak responses across different countries.

The project is based on a consortium encompassing many of the countries at risk of Ebola virus outbreaks. Initially, it focuses on two particularly high-risk countries, the DRC and Guinea. It places a strong emphasis on preparedness, including the development and approval of a standardised clinical trial protocol that can be immediately implemented when outbreaks occur. Other key activities include ensuring that monoclonal antibody and other trial supplies will be immediately available and the preparation of clinical trial sites. 

The project also includes a strand of work on community engagement to identify potential issues that might affect trial conduct and to ensure community support for research activities.

Impact

The EBO-PEP project will generate critical data on the effectiveness of monoclonal antibody PEP for Zaire ebolavirus. It will:

• Provide policymakers with key evidence on the effectiveness and cost-effectiveness of monoclonal antibody PEP to inform national Ebola outbreak response strategies.
• Build capacity for clinical care of Ebola virus patients and clinical research on Ebola virus and other emerging infections.
• Provide a model for innovative coordinated, multi-country, multi-outbreak clinical trials for emerging and re-emerging diseases.

If the effectiveness of monoclonal antibody PEP is confirmed, it would provide a way to protect those at highest risk of Ebola virus infection, including household contacts and healthcare workers, leading to reduced mortality and more rapid containment of outbreaks.