A global health crisis demands swift, yet scientifically sound, action. In the wake of a concerning outbreak of Ebola disease caused by the Bundibugyo virus (BVD) affecting the Democratic Republic of the Congo and neighboring Uganda, the World Health Organization (WHO) has brought together leading experts. Their crucial advice underscores a critical point: while promising treatments and vaccines are on the horizon, they must first undergo rigorous evaluation within clinical trials to ensure they are safe, effective, and ethically sound for public use. ## Unpacking the Bundibugyo Virus Outbreak Ebola is a severe, often fatal, illness caused by the Ebola virus. While most people are familiar with the Zaire ebolavirus, responsible for the largest and most widely recognized outbreaks, there are several species within the Ebolavirus genus. The Bundibugyo virus is one such species, causing similar devastating symptoms that include fever, severe headache, muscle pain, fatigue, diarrhea, vomiting, abdominal pain, and unexplained bleeding. Like other Ebola viruses, it spreads through direct contact with blood, bodily fluids, or contaminated objects, often posing a significant threat to healthcare workers and family members caring for the sick. The current outbreak in DR Congo and Uganda highlights the urgent need for specific medical tools to combat this particular strain, as existing interventions for other Ebola types may not be fully effective. Recognizing this urgent need, the WHO initiated a series of meetings involving its R&D Blueprint technical advisory groups, dedicated to fast-tracking research and development during epidemics. Additionally, the Strategic Advisory Group of Experts on Immunization (SAGE) and its Ebola vaccine working group were convened. These expert gatherings are vital for assessing potential countermeasures and guiding the global health community on the most responsible path forward. ## Promising Treatments Under Review Currently, no specific treatments or vaccines are officially licensed to prevent or cure Ebola disease caused by the Bundibugyo virus. However, the expert panels identified several promising candidates that warrant immediate investigation through clinical trials. For individuals already infected with BVD, the focus is on three key therapeutic agents: Firstly, two monoclonal antibodies, **MBP134** and **Maftivimab®**, have been prioritized. Monoclonal antibodies are lab-made proteins that mimic the body's natural immune response. They are designed to target and neutralize the virus, helping the immune system fight off the infection. The idea is to give the body a strong, specific defense against the invading virus. Secondly, the antiviral medication **remdesivir** was also recommended for evaluation. Antivirals work by interfering with the virus's ability to replicate within human cells, thereby slowing down or stopping the infection's progression. Experts also suggested exploring combination therapy, where a monoclonal antibody is used alongside remdesivir, to potentially enhance treatment effectiveness. ## Advancing Prevention Strategies Preventing the spread of Ebola is equally critical. For those who have been exposed to a confirmed or probable case, a strategy known as post-exposure prophylaxis (PEP) is being considered. The oral antiviral **obeldesivir** was identified as a priority candidate for PEP. This approach involves giving tablets of obeldesivir to contacts of infected individuals to see if it can prevent them from developing Ebola disease. While promising, experts noted that the success of PEP heavily relies on effective contact tracing, which can be logistically challenging in some affected regions of the Democratic Republic of the Congo. Vaccines represent another cornerstone of prevention. Two candidate vaccines specifically targeting the Bundibugyo virus are under intense scrutiny. The single-dose **rVSV Bundibugyo vaccine**, under development by the International AIDS Vaccine Initiative (IAVI), shows significant promise. However, it will likely take 7–9 months before it is ready for assessment in a clinical trial. Another candidate, the **ChAdOx1 Bundibugyo vaccine** from Oxford University/Serum Institute of India, might be ready for efficacy assessment within 2–3 months. Experts are still awaiting additional animal data to fully prioritize this vaccine, which could be administered as a single dose for contacts or a two-dose strategy for high-risk, unexposed populations like healthcare workers. ## The Role of Existing Ebola Vaccines The discussions also touched upon **Ervebo**, the only licensed Ebola vaccine, approved for outbreaks caused by the more common Zaire ebolavirus. While Ervebo has been instrumental in controlling Zaire ebolavirus outbreaks, its effectiveness against the Bundibugyo virus is not yet established. Evidence regarding its cross-protection against other Ebola virus species remains limited and inconclusive. Therefore, WHO advises that Ervebo should not be used outside carefully designed research settings when dealing with BVD, allowing its performance against this specific strain to be properly evaluated. ## Ensuring Ethical and Safe Clinical Trials The commitment to scientific rigor goes hand-in-hand with ethical responsibility. WHO, in collaboration with the governments of the Democratic Republic of the Congo and Uganda, the Africa Centres for Disease Control and Prevention (Africa CDC), ANRS Emerging infectious diseases (French National Agency for Research on AIDS and Viral Hepatitis), and other scientific partners, is working diligently to develop and implement appropriate protocols for these clinical trials. The aim is to assess the safety and efficacy of these prioritized therapeutics and vaccines through robust field trials. It is paramount that all research adheres to the highest ethical standards, guided by national health authorities and in close consultation with the affected communities. This includes ensuring informed consent, protecting participant rights, and transparently sharing research findings. Beyond research, WHO emphasizes the need for accelerated access to essential supplies, stronger community protection measures, ongoing engagement and trust-building with local populations, and coordinated investment in the research, development, and evaluation of BVD countermeasures. ## The Bedrock of Ebola Response While new treatments and vaccines are being developed, the immediate priority remains stopping transmission with established public health tools. These include vigilant disease surveillance, rapid testing and diagnosis to identify cases swiftly, thorough contact tracing to monitor those exposed, immediate isolation and compassionate care for patients, stringent infection prevention and control measures in healthcare settings, active community engagement to foster understanding and cooperation, and safe and dignified burial practices to prevent further spread. These foundational strategies have been the backbone of Ebola response for decades and continue to be essential in controlling the current Bundibugyo outbreak while the scientific community works towards new, targeted solutions.