Marburg outbreak: Why isn’t there an approved vaccine for the deadly, Ebola-like disease?

An outbreak of Marburg, a virus closely related to Ebola that can cause severe and often fatal disease, is spreading in Rwanda. As Africa struggles with compounding public health challenges, this one presents a rare silver lining: the chance to test new vaccines that could save lives across the continent in the future.

The first patient infected with the virus in the country died on September 8, the World Health Organization (WHO) said at a press conference Thursday. As of September 29, a total of 36 cases and 11 deaths have been reported, making it one of the largest Marburg outbreaks in history. Although most infections are among health care workers from two hospitals in Kigali, the capital of the East African country, seven of Rwanda’s 30 districts have seen cases. It is the first time the virus has been known to cause infections in Rwanda.

The WHO indicated the outbreak is highly likely to spread to neighboring countries, but the risk of further global spread is low. Typically, humans become infected when they come into contact with a Marburg-carrying Egyptian fruit bat, a species found across Africa, the Middle East, and parts of western Asia. Once a person has the virus, though, it can then spread to others through contact with bodily fluids or contaminated surfaces and materials, like clothing or bedding. This mode of transmission means that Marburg virus will not spread as easily as, say, Covid-19 or other respiratory diseases.

However, as we have seen in previous Marburg virus outbreaks, travelers returning from countries experiencing an outbreak can introduce the disease into their home countries. Already, one person who came into contact with an infected patient in Rwanda has traveled to Belgium, underscoring the possibility of isolated overseas cases.

Historically, Marburg virus disease is fatal in about 50 percent of patients, but in some previous outbreaks, the mortality rate has exceeded 80 percent. People experience high fever, severe headache, extreme fatigue, rash, bloody diarrhea, abdominal cramping, and unexplained bruising and bleeding from the nose and gums. Symptoms can appear anywhere from 2 to 21 days after the initial infection.

All previous Marburg virus outbreaks have occurred in sub-Saharan Africa, most recently in Tanzania, where there were eight confirmed cases and five deaths, and in Equatorial Guinea, where there were 16 confirmed cases and 12 deaths; both outbreaks occurred in 2023. Between 1967 and 2008, the US, Germany, Yugoslavia, and the Netherlands have reported Marburg disease among travelers returning from Uganda.

To date, there is no approved treatment or vaccine for Marburg virus disease, but there are at least four vaccines in development. All four have been effective in studies involving animals. A small, early-stage clinical trial in humans had promising results; however, study participants who received the Marburg vaccine were not exposed to the virus to test how protective the shot was. Two other vaccines for Ebola virus could also be effective against Marburg virus.

Researchers in Rwanda are preparing to submit protocols for phase 3 trials to a Rwandan ethics committee for approval. This would be an opportunity to expedite the development of Marburg virus vaccines and treatments and perform larger trials in a real-world outbreak.

If the trial moves forward quickly, the current crisis could allow scientists to identify a shot that protects millions of people in the years to come.

The WHO, Rwandan public health officials, and a group of scientists and institutes working on vaccine research met earlier this week to discuss quickly setting up a vaccine trial that could help quell the ongoing outbreak.

Of the vaccine candidates being developed, the most promising one that seems most likely to be tested if a trial moved ahead in Rwanda is the cAd3-Marburg vaccine developed by the National Institute of Allergy and Infectious Diseases (NIAID). Last year, the NIAID tested the vaccine for safety in humans for the first time in a phase 1 clinical trial.

Forty healthy adults received one of two different doses of the vaccine and were monitored for adverse reactions and to see if their immune systems produced antibodies, an indication that the vaccine would be effective if the individuals were exposed to the virus. The vaccine was deemed safe, and 95 percent of the participants had developed antibodies four weeks after receiving it. However, the participants were never exposed to the virus, so the vaccine’s practical effectiveness was not evaluated.

Earlier this year, the Sabin Vaccine Institute started a phase 2 clinical trial for the NIAID vaccine in Uganda and Kenya. Healthy adults will randomly be assigned to receive the vaccine or a placebo shot and then will again be monitored for adverse responses and antibody responses. Participants will also not be exposed to the Marburg virus during this trial.

Typically, if phase 2 trials are successful, scientists proceed to larger phase 3 trials and roll out the vaccine to a large group of people and then observe its impact when individuals are exposed to the virus. The emergency situation in Rwanda may accelerate this process. Scientists may move ahead with a phase 3 trial even though phase 2 results are not yet available.

Researchers and health officials have been preparing for this. Earlier this year, scientists from the WHO and 17 countries at risk for Marburg virus outbreaks developed protocols to test both vaccines and treatments during an outbreak. A phase 3 clinical trial in Rwanda would follow a ring vaccination strategy where contacts of infected people are vaccinated. The trial would have two groups, one group of contacts who are immediately vaccinated and then a second “delayed” group who are presumably vaccinated at a later time. Researchers would then compare the impact of the vaccine between the two groups.

Scientists may also test a treatment that uses antibodies, proteins made by the immune system to kill viruses and other pathogens, against the virus. One study found that treating animals such as guinea pigs and monkeys with these antibodies after they were infected with Marburg virus prevented serious illness and death. Medical workers successfully treated patients with antibody cocktails during previous Ebola virus outbreaks.

The WHO’s ethics committee has already approved protocols to test vaccines and the antibody treatment, a spokesperson told Vox. The next step is for these protocols to be approved by an ethics committee within Rwanda. Two Rwandan researchers have been selected to lead these efforts in the country.

One other hurdle remains. There are fewer than 2,000 total vaccine doses currently available. In April 2023, the Sabin Vaccine Institute had produced about 850 of those doses. Oxford University, which is developing another Marburg vaccine, had about 1,000 doses. Larger-scale production could be needed, especially if the outbreak becomes more widespread. Both the Sabin Vaccine Institute and Oxford University have existing manufacturing capacity for the Marburg vaccines and previously reported to the WHO that they could rapidly produce additional doses.

The Marburg outbreak has ignited amid a surging mpox outbreak in the region, which the World Health Organization declared an international health emergency in August. The Democratic Republic of the Congo, which neighbors Rwanda, is the epicenter of the mpox outbreak. (The DRC has not yet recorded any Marburg cases.)

Fortunately, Rwanda has one of the strongest public health systems in Africa and has only reported a handful of mpox cases. An estimated 90 percent of the population have health insurance, much higher than most of its neighbors. Rwanda also has a strong infectious disease surveillance system and a history of successfully containing outbreaks.

That makes it an ideal setting for testing a Marburg vaccine during the current outbreak — if public health authorities can move quickly. The race is on.