Overview

The BRAVO study (Bundibugyo: Respondre Avec la Vaccination, "On est ensemble") was developed in response to the 2026 Bundibugyo virus disease (BVD) outbreak in the Democratic Republic of the Congo (DRC). The study focuses on frontline workers (FLWs), who are at increased risk of infection because of their involvement in patient care, outbreak response activities, and contact with affected communities. Protecting this population is critical for maintaining healthcare services and strengthening outbreak control efforts.

Currently, there is no licensed vaccine specifically targeting Bundibugyo virus (BDBV) for broad use. However, ERVEBO®, a vaccine licensed against Zaire ebolavirus, is available and has demonstrated a favorable safety profile. Although preclinical and immunological evidence suggests that ERVEBO® may provide some degree of cross-protection against BDBV, the extent of protection remains uncertain. BRAVO therefore aims both to support rapid vaccination of frontline workers during the outbreak and to generate evidence that can inform future vaccine policy and preparedness strategies.

BRAVO is designed as a phased study embedded within the public health response. The study population includes adults aged 18 years and older working in Ebola treatment centers, healthcare facilities, or community-based outbreak response activities in affected areas. Both clinical and non-clinical personnel may participate if their duties place them at risk of exposure to infected individuals, infectious materials, or affected communities.

The study consists of three steps:

Step A: Immediate deployment and evaluation of ERVEBO® during the outbreak. Step B: Potential future evaluation of heterologous prime-boost vaccination strategies if additional vaccines become available and remain relevant.

Step C: Potential contribution to evaluation of future Bundibugyo virus-specific vaccines.

The primary focus of the current study is Step A, which is a prospective cohort study conducted under real-world outbreak conditions. The main objective is to assess the effectiveness of ERVEBO® vaccination against Bundibugyo virus disease, severe disease outcomes, and death. The primary effectiveness endpoint is whether vaccination reduces case fatality among laboratory-confirmed BVD cases hospitalized in Ebola treatment facilities.

Secondary objectives include evaluating whether vaccination reduces:

BVD-related mortality in the cohort, Incidence of symptomatic laboratory-confirmed BVD, Indicators of severe disease among confirmed cases.

Safety is also an important component of the study. Serious adverse events occurring within one month after vaccination will be documented, and pregnancy outcomes among enrolled pregnant participants will be monitored.

Participants may be enrolled regardless of vaccination status, allowing comparisons between vaccinated and unvaccinated frontline workers as vaccine deployment progresses according to operational feasibility and risk prioritization. Written informed consent will be obtained before enrollment and vaccination. The consent process will clearly communicate that protection against Bundibugyo virus has not been established and that additional vaccine options may become available in the future.

Participants will generally be followed for six months after enrollment, or until the end of the outbreak if it occurs earlier. Pregnant participants will be followed through pregnancy outcomes. An additional component within Ebola treatment centers will collect information on frontline workers presenting with symptoms compatible with BVD, supporting supplementary analyses of vaccine effectiveness using routinely collected clinical and laboratory data.

Step A aims to vaccinate approximately 20,000 frontline workers during the first six months of implementation. Based on projected outbreak assumptions, the study may generate sufficient confirmed BVD cases to provide meaningful estimates of vaccine effectiveness, particularly regarding protection against death.

Beyond evaluating the immediate impact of vaccination, BRAVO is expected to strengthen outbreak preparedness by establishing systems for vaccination delivery, pharmacovigilance, data collection, and participant communication. The study is designed to provide decision-relevant evidence during the outbreak rather than after it, helping guide future recommendations for Bundibugyo virus vaccine strategies.

Enrollment and vaccination are planned from September through December 2026, with follow-up continuing through June 2027. Final analysis and reporting are expected in September 2027.

Eligibility

Eligibility criteria for enrolment in the BRAVO cohort

Inclusion criteria:

The following FLWs will be eligible for enrolment in the study:

• Aged 18 years or older
• Currently working, or holding a signed work assignment to work, in the following settings within BVD-affected study areas:
  • Ebola health facilities, including physicians, nurses, nurse assistants, laboratory technicians, pharmacists, IPC personnel, environmental hygiene and waste management personnel, mental health and psychosocial support staff, cleaners, security personnel, administrative and any other potentially exposed staff
  • Health facilities providing non Ebola clinical care, including but not restricted to services such as emergency care, general outpatient or inpatient care, surgery, laboratory services, maternity, haematology, infectious diseases, paediatrics
  • Community based or outbreak response activities, including surveillance and contact tracing teams, drivers and ambulance teams, vaccination teams, community health workers and personnel responsible for post mortem swabbing or burial related activities
  • Any other personnel whose duties involve direct contact with suspected or confirmed Ebola cases, their bodily fluids, contaminated materials, or environments where Ebola transmission may occur.
• Able and willing to complete the informed consent process and comply with study procedures

Exclusion criteria :

There are no exclusion criteria to participate in the BRAVO cohort. If a FLW chooses to not receive the ERVEBO vaccine, they can be enrolled as part of the control group.

To be part of the vaccinated group, additional criteria apply as below:

Eligibility criteria specific to vaccination

Inclusion criteria:

• Enrolled in the BRAVO study (eligible and gave informed consent)
• Voluntary chooses to receive vaccination

Exclusion criteria:

• Voluntarily chooses not to receive vaccination
• Self reported clinically significant immunodeficiency (e.g. a known immunodeficiency condition that, in the judgment of the study clinician, may affect the safety and effectiveness of ERVEBO® vaccination, such as HIV infection with an AIDS-defining illness, CD4+ T-lymphocyte count \<200 cells/mm³, HIV/AIDS or another severe immunocompromising condition). Stable HIV infection on antiretroviral therapy with preserved immune function is not a contra-indication)
• History of severe allergic reaction or anaphylaxis associated with a vaccine or vaccine component
• Any other condition or reason not otherwise specified in the protocol which, in the opinion of the investigator or delegated clinician, would contraindicate administration of ERVEBO® or make vaccination inappropriate. Any decision to withhold vaccination on this basis will be documented, including the rationale for exclusion.