Q&A: Behind the Marburg Virus Outbreak in Rwanda

Sabin’s rapid delivery of investigational vaccines during Rwanda’s Marburg outbreak showcased exceptional coordination among all the partners. This Q&A unpacks the timeline, Sabin’s role, the clinical trial, the vaccine candidate, and key lessons for future collaborations.

1. When did the 2024 Marburg outbreak in Rwanda officially start and when did it end?

On September 27, Rwanda declared a Marburg virus outbreak, mainly affecting healthcare workers after a mine worker— the index case— was linked to a hospital cluster. The last Marburg patient was discharged on November 8, and the outbreak was declared over on December 20.

With 66 confirmed cases and 15 deaths, the case fatality rate was 22.7%, much lower than previous Marburg outbreaks which have had fatality rates as high as 88%.

2. What was Sabin’s role in the outbreak?

To support Rwanda’s outbreak response, Sabin provided approximately 2,700 investigational Marburg vaccine doses . These vaccines were used in two arms of a clinical trial sponsored by the Rwanda Biomedical Centre (RBC).

1. The first shipment of ~700 doses was delivered just nine days after the outbreak was declared, enabling vaccinations to begin the next day in a rapid-response single-arm trial (RBC-001, Part A). The timeline from outbreak declaration to vaccinations: 10 days. 
2. A second shipment of ~1,000 doses followed a week later, supporting the single-arm trial and bringing the total to approximately 1,700 vaccines administered in this phase.
3. A third shipment of ~1,000 doses arrived in November for a randomized trial arm (RBC-001, Part B) but have not been used (see below) and are currently being stored in Rwanda.

3. How did Sabin become involved?

On September 26, Rwandan President Paul Kagame’s team contacted Sabin CEO Amy Finan directly for assistance. Sabin then connected with the Rwanda Biomedical Centre (RBC), the Coalition for Epidemic Preparedness Innovations (CEPI), IQVIA, and other Rwanda government officials to form a working group. Meeting daily over the course of the outbreak, this group quickly adapted Sabin’s current Phase 2 Marburg protocol (developed for trials in Kenya and Uganda) for use in the Rwanda outbreak. Sabin also coordinated closely with its funding partner, the Biomedical Advanced Research and Development Authority (BARDA). This enabled RBC, the trial sponsor, to secure swift approval from the Rwandan ethics committee and the U.S. Food and Drug Administration (FDA) for the first part of the trial (RBC-001, Part A).
Sabin’s experience in developing vaccines for filoviruses, including its ongoing Phase 2 programs for both Marburg and Sudan ebolavirus vaccines, enabled it to mount a swift response. Additionally, Sabin is a long-standing member of MARVAC, a WHO-coordinated consortium that promotes international collaboration on developing Marburg virus vaccines.

4. How were vaccines delivered to Rwanda within 9 days of the outbreak?

The rapid response was enabled by several factors:

1. Partnership with the Rwandan government: Rwanda led an expeditious outbreak response, streamlining processes to meet urgent timelines and leveraging its strong health care system.
2. Ongoing Phase 2 trials: Sabin’s active Marburg vaccine trials in Uganda and Kenya facilitated quick preparation of trial documentation for Rwanda review and approval.
3. Prepared vaccine stock: Sabin and its contract manufacturer ReiThera had doses ready for immediate deployment, streamlining packaging, labeling, international shipping and supporting documentation to support these actions.
4. Funding support: BARDA, which funds Sabin’s Marburg (and Sudan ebolavirus) vaccine development program, was prompt in approving Rwanda’s request for vaccine.
5. Strong partnerships: Sabin’s established relationships with key partners, including CEPI, ensured coordinated efforts.

5. What did the clinical trial entail?

The Phase 2 rapid response open-label trial, RBC-001 Part A, began with a single-arm protocol for adults aged 18 years and older in an outbreak setting. High-risk individuals, primarily healthcare workers, were vaccinated at multiple trial sites with Sabin’s single-dose cAd3-Marburg vaccine. All subjects enrolled in the study received the investigational Marburg vaccine.

RBC-001 Part B is the amended version of the original protocol and enables a randomized trial arm aimed at enrolling approximately 1,000 at-risk individuals, including mine workers. According to the amended protocol, additional participants would have been randomized 1:1, with half receiving the vaccine immediately and the other half 21 days later, aligning with the disease’s incubation period. RBC-001 Part B has not been initiated because the outbreak was subsiding by the time it could have been implemented.

6. Why did Rwanda decide to opt for a single-arm trial protocol first?

Healthcare workers were disproportionately affected by the Marburg virus during the outbreak, with some losing their lives to this deadly disease. As a result, Rwanda leaders weighed the risks and benefits of various response scenarios. Based on the outbreak’s specific dynamics, they chose to prioritize the safety of health care and other frontline workers by implementing an open-label, single-arm trial, where all participants received Sabin’s investigational Marburg vaccine. In addition to healthcare and frontline workers, high-risk contacts of confirmed cases within the virus’s 21-day incubation period were also enrolled.

As an investigational product, the Sabin Marburg vaccine requires rigorous safety monitoring and data collection to support its advancement toward licensure. With IQVIA’s support, the RBC-001 clinical study adheres to Good Clinical Practices, ensuring the highest standards in research and participant safety.

7. Who is the sponsor of the clinical trial?

RBC is the sponsor of RBC-001 and, with IQVIA as its contract research organization and partner, is responsible for all aspects of the trial including data analysis. Sabin provided its vaccine in accordance with RBC-001, as reviewed and approved by Rwandan ethics and regulatory authorities. Sabin’s clinical trial agreement with RBC is based on Sabin’s Clinical Partnership Framework.

8. What does the clinical trial hope to learn?

The single-arm (RBC-001, Part A) trial assesses the vaccine’s safety, tolerability, and immunogenicity. The randomized arm (RBC-001, Part B) aimed to evaluate efficacy.

9. How does the vaccine work?

Sabin’s Marburg vaccine is designed to protect people from getting sick before they are exposed to the virus. While the vaccine is still in the investigational stages, early testing shows promising results.

The vaccine uses a harmless version of a virus to deliver instructions to the body. These instructions help the body produce a protein from the Marburg virus, which then trains the immune system to recognize and fight the virus.

In early trials, nearly all participants developed antibodies against Marburg within two weeks, and everyone showed a strong immune response by four weeks. Studies in animals also showed that the vaccine could create a protective immune response.

10. Is this a single dose or two-dose vaccine? 

This is a single-dose vaccine.

11. Can this vaccine be used in children? 

So far, the investigational vaccine has only been evaluated in adults aged 18 years and older. There are no immediate plans to test this among children.

12. Based on Phase 1 trials and non-clinical studies, how safe is this vaccine? 

The cAd3-Marburg vaccine was safe and well-tolerated in Phase 1 trials, with no serious adverse events reported among 56 participants. Additionally, over 150 non-human primates showed no signs of toxicity after vaccination. The cAd3 platform has been tested in over 5,000 participants, including children, across various studies.

13. What is next for the Sabin Marburg vaccine candidate?

Interim results from the Phase 2 Marburg vaccine trial in Uganda and Kenya are expected next year. A similar-stage trial is expected to be conducted in the U.S in 2025.

Sabin remains committed to advancing filovirus vaccine development, supported by funding partners like BARDA and through collaborations with organizations such as MARVAC.

14. What lessons can inform future outbreak response? 

Each outbreak is unique, but this response highlights the importance of trusted partnerships and preparedness.

Centered on science and local leadership, Sabin’s approach underscores the importance of following the virus while listening to country-level health officials who understand their communities and systems. The vaccination strategy was a direct result of this collaboration.

Rwanda’s ability to manage public health crises also played a key role. The country utilized early warning systems, AI-powered disease modeling, expanded health facilities, and mobilized its dedicated community health workers to contain the outbreak effectively.