BRAVO study: Prospective evaluation embedded in the Bundibugyo virus disease outbreak response in the Democratic Republic of Congo
Design
- Interventional study
- Prospective quasi experimental study with a nested case-control test negative design
Why BRAVO is needed
BRAVO was developed in response to the 2026 Bundibugyo virus disease (BVD) outbreak in the Democratic Republic of the Congo. Frontline workers (FLWs) are among the groups at highest risk because they are exposed through clinical care, outbreak response work, and contact with affected communities. Protecting FLWs is important both for their own safety and for continuity of health services and outbreak control.
At present, no Bundibugyo virus (BDBV)-specific vaccine is available for broad use. However, ERVEBO®, a vaccine licensed against Zaire ebolavirus, is available in substantial quantities and has a well-established safety and operational profile. Preclinical data and recent human immunology data suggest that ERVEBO® may induce some cross-reactive immunity against BDBV, but the degree of protection is uncertain.
BRAVO therefore aims to do two things at the same time:
• support rapid vaccination of FLWs during the outbreak response, and
• generate evidence that can inform policy on interim vaccine strategies against BVD.
Our role
- Coordination
Partners
- Ministère de la Santé of the Democratic Republic of Congo
- University of Kinshasa (UNIKIN)- Institut national de recherche biomédicale (INRB), Institut national de santé publique (INSP), Programme Elargi de vaccination (PEV), School of Public Health
- MSF
- CDC Africa
Overall study approach
BRAVO is designed as a phased study embedded within the outbreak response. Its main emphasis is Step A, which evaluates immediate deployment of ERVEBO® under real-life conditions.
The study population includes FLWs aged 18 years and older working in Ebola treatment centers, health facilities, or community-based outbreak response activities in BVD-affected areas. This includes both clinical and non-clinical personnel whose work may expose them to patients, infectious materials, or affected communities.
BRAVO has three steps:
• Step A: immediate deployment and evaluation of ERVEBO®.
• Step B: possible later evaluation of heterologous prime-boost strategies if another vaccine becomes available and remains relevant.
• Step C: potential contribution to evaluation of future BDBV-specific vaccines.
These three phases share a common basic structure, but have different objectives and sub-components. Phase A is the first to begin (September 2026). The details of Phases B and C are currently being finalised, and their specific objectives are not yet included on this page.
Step A: what the study will assess
Step A is a prospective study of FLWs conducted during rollout of ERVEBO® in outbreak settings. The main goal is to assess the real-world effectiveness of vaccination against BVD, severe disease, and death.
The primary effectiveness question is whether ERVEBO® reduces case fatality among laboratory-confirmed BVD cases hospitalized in Ebola health facilities.
Secondary objectives include assessing whether vaccination reduces BVD-attributable deaths in the cohort, reduces the incidence of symptomatic laboratory-confirmed BVD, and reduces markers of severe disease among confirmed cases.
Step A also includes safety objectives. Serious adverse events will be documented in vaccinated FLWs for one month after vaccination. Pregnancy outcomes will also be documented among included pregnant women.
Step A design in practice
The core design is a prospective cohort under routine outbreak conditions. Both vaccinated and unvaccinated FLWs can be enrolled, allowing comparison of outcomes over time as vaccine rollout progresses according to feasibility and risk prioritization.
Schematic view (Step A, Ervebo vaccination)
Written informed consent will be obtained before enrolment and vaccination
The consent process will explicitly explain that protection against BDBV is uncertain, that no licensed BDBV-specific vaccine is yet broadly available, and that other vaccines may become available later. This is important to avoid misunderstanding and to maintain infection prevention and control practices.
Participants will generally be followed for six months after enrolment, or until the declared end of the outbreak if this occurs earlier. Pregnant participants will be followed through pregnancy outcomes. If the outbreak continues, follow-up may be extended.
An embedded Ebola treatment centre component will also collect data on FLWs presenting with symptoms compatible with BVD. This will support additional vaccine effectiveness analyses, including a test-negative approach based on routine clinical and laboratory data.
Scale and expected contribution
The target for Step A is approximately 20,000 FLWs vaccinated during the first six months, with possible continuation if the outbreak persists. Under the assumptions presented in the synopsis, this could yield around 200 confirmed BVD cases among vaccinated FLWs, which would provide useful precision for estimating vaccine effectiveness against case fatality.
The study is intended to produce decision-relevant evidence during the outbreak rather than after it. Beyond the immediate findings, BRAVO will also help establish operational infrastructure for vaccination, pharmacovigilance, data systems, and communication tools that could support future outbreak responses.
