An Ebola-like virus is spreading in Rwanda. Why isn’t there an approved vaccine for Marburg?

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 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 October 8, a total of 56 cases and 12 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 28 vaccines in various stages of development, four of which have been prioritized by the WHO. 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.

Immediately after the first Marburg cases were reported, Rwandan health officials and the World Health Organization started coordinating with a consortium of researchers and vaccine manufacturers to hold clinical trials for these vaccines. This week, the first doses reached the country, and health care workers have started receiving the vaccine. If the trials are successful, then scientists will finally have tools to swiftly quell and even prevent future Marburg crises.

Of the four Marburg vaccines that researchers have been developing, the cAd3-Marburg vaccine developed by the National Institute of Allergy and Infectious Diseases (NIAID) had progressed further in clinical trials before the current outbreak began. 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. But the participants were never exposed to the virus, so the vaccine’s practical effectiveness — as in how well it prevented severe disease and death — 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. Like in previous studies, participants will not be exposed to the Marburg virus during this trial.

This is typical of early stage clinical trials. Phase 1 and Phase 2 trials focus primarily on evaluating the safety of a new vaccine or drug and making sure that the vaccine triggers the immune system. (A vaccine’s ability to trigger the immune system does not equate exactly to being able to prevent severe illness or death.) During these trials, the vaccine or drug is given only to healthy people, usually adults, in controlled clinical environments. Normally, during these early trials, study participants are not exposed to the pathogen that the vaccine or treatment protects against. That doesn’t happen until Phase 3 trials when thousands of volunteers randomly receive either the vaccine or treatment being tested or a placebo and then leave the clinic to live their normal lives. Researchers follow the study participants to see if there is a difference in disease severity or other outcomes between the two groups.

Testing vaccines for Marburg virus disease presents a particular challenge because the disease usually pops up unexpectedly and quickly ignites into a deadly outbreak. Like with Ebola, researchers can try to roll out a trial in the middle of an outbreak. That is exactly what public health officials and vaccine manufacturers are doing right now amid the emergency situation in Rwanda.

On Saturday, 700 vaccine doses arrived in Rwanda. So far, health care workers in Rwanda — who make up the majority of infections and have historically been at high risk of Marburg infection — have started receiving the vaccine.

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. The protocols described a ring vaccination strategy where contacts of infected people are vaccinated.

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. There will also be a trial for the antiviral drug Remdesivir, which was used during the Covid-19 pandemic, said Sabin Nsanzimana, the minister of health in Rwanda, during a press conference last week.

The WHO’s ethics committee had already approved protocols to test vaccines and the antibody treatment before the outbreak began, a spokesperson told Vox. Last week, a Rwandan ethics committee approved a phase 2 trial protocol for the Marburg vaccine. Because of the deadly threat the virus poses to health care workers, all study participants will receive the vaccine. No one will receive a placebo.

One other potential hurdle remains. Before the outbreak, there were fewer than 2,000 total vaccine doses 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. However, the Sabin Vaccine Institute has already produced another thousand doses which will arrive in Rwanda later this week, a spokesperson for the Sabin Vaccine Institute told Vox.

The Marburg outbreak has ignited amid a surging mpox outbreak in the region, which the WHO 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. That local and international scientists have been able to coordinate trials so quickly is unprecedented and marks a huge milestone in outbreak response.

Update, October 9, 10:37 am: This story was originally published on October 4 and has been updated to include the number of deaths so far, information about the newly initiated trial in Rwanda, and how this trial differs from a traditional clinical setting.