Infectious diseases | Dispute over “hope” in the Ebola epidemic

Bunia, capital of Ituri Province: Waiting for subjects in the Tumaini vaccine study Photo: IMAGO/Xinhua Tumaini means hope in Swahili. For a few weeks now, the word from the language widespread in East Africa, which is also one of the official languages ​​in the Democratic Republic (DR) of Congo, has had a further meaning: This is the name of the platform study launched by the World Health Organization (WHO) at the end of October to test whether vaccines are safe and effective against the Bundibugyo Ebola virus that is rampant in the country. The advantage: Thanks to the existing infrastructure, different vaccines can be tested at the same time. Time is of the essence because the numbers continue to rise unabated from week to week, while two other countries have also reported their first cases.

With the serious outbreak in the DR Congo, the international community was caught on the wrong foot. Although the WHO declared an international health emergency in May, there were neither medications, diagnostics nor vaccines against Bundibugyo. This virus caused an outbreak almost 20 years ago. However, the only vaccine available was the Ervebo vaccine from the US pharmaceutical company Merck, which was approved in 2019 for the Zaire variant of the Ebola pathogen, and which was used two years later to establish a global emergency reserve that is managed by a coordination group under the umbrella of the WHO. 336,000 cans are stored here.

Now tests have finally started. Tumaini is led by the Institut National de Recherche Biomedicale in the capital Kinshasa and the University of Antwerp. In addition to the WHO, the African Union and Doctors Without Borders are also involved. It started with Ervebo. Animal experiments and laboratory tests had provided initial indications of the vector-based live vaccine that it could possibly offer cross-protection with Bundibugyo.

Tumaini is a combined phase 2 and 3 study for which a total of 20,000 Ervebo doses are available. Side effects and the correct dose as well as effectiveness are tested. Test subjects should be identified contact persons of infected people. The plan is for one group to receive a dose immediately, people in the control group to first receive a placebo (a typhoid vaccine) and also a dose of Ervebo on the 29th day. “It is the most ethical study design possible – everyone who takes part in it will receive a vaccine candidate against the Bundibugyo virus,” says co-leader Jean-Pierre Van Geertruyden. The first results are not expected before the beginning of 2027.

However, the study design is controversially discussed among experts. Especially in view of the acute need: More than four million people live in the province of Ituri alone, the actual epicenter. As many as 66 health centers in eight provinces of the huge Central African country are now affected. “We are currently talking about dozens of individual outbreaks,” says Daniel Bausch, an expert in tropical medicine and global health.

The government of the DR Congo has therefore called for Ervebo to be released for regular vaccination campaigns even without clinical tests. Aid organizations are also calling for a faster response because the vaccine is safe. Holding him back beyond the study would be negligent.

The WHO rejects this: An advisory group stated that, based on current knowledge, protection against fatal outcomes may be possible, but not against disease and transmission. Mass vaccination could have significant negative consequences for the already weak health system in the affected areas. A vaccination with a vaccine that turns out to be potentially ineffective could also trigger reckless behavior and ultimately only further fuel the already existing vaccination skepticism locally. “Everything is going well at the moment – ​​people want to be vaccinated,” says Geertruyden, advocating the strict study design. “We have to ensure that we maintain this momentum.” However, the WHO is taking the pressure into account by earmarking an additional 50,000 doses for medical staff outside of the study.

Nevertheless, Doctors Without Borders (MSF), which is active in all areas with particularly high transmission rates, launched its own study in September called “Bundibugyo: Répondre Avec la Vaccination” (BRAVO): In this “response with vaccination,” up to 20,000 health workers will be vaccinated in collaboration with local partners. If Ebola symptoms later appear among medical staff in the treatment centers, the actual effectiveness is determined based on the PCR status (positive vs. negative) and the documented vaccination status. With this “test-negative design,” MSF is less concerned with a clean scientific study than with quick protection for the endangered medical staff “on the front lines.” Bravo will provide “real-world insights into whether Ervebo protects against illness and death caused by the Bundibugyo virus,” said the NGO.

"Vaccines alone will not end this outbreak, but they could become a powerful new tool to bring it under control."

At the same time, Doctors Without Borders warns of production bottlenecks at Ervebo: Merck must “make all doses produced in the coming months available to the global vaccine supply,” demands Julien Potet, MSF expert on access to vaccines. At the same time, high-income countries should refrain from reserving doses beyond their immediate public health needs. And given the significant public resources allocated to the development of bundibugyo-specific vaccines, they would need to be “made accessible and affordable” to all populations affected by outbreaks.

In fact, after the health emergency was declared, hectic activity began among international organizations. The “Coalition for Epidemic Preparedness Innovations” invested tens of millions of US dollars in rapid vaccine research and development. The Gavi vaccine alliance, in turn, provided $50 million, among other things, to expand production.

At least four vaccines specifically for Bundibugyo are currently in the pipeline, two of which were recently included in the Tumaini study: a vaccine developed by the University of Oxford together with the Serum Institute of India, which is similar to Astra Zeneca's vector vaccine from the Corona era, and an mRNA vaccine from the US company Moderna. "One problem is that it takes months rather than weeks until phase I data is available, vaccine doses are produced and the vaccines can be included in the study," explains Jürgen May, CEO of the Bernhard Nocht Institute for Tropical Medicine in Hamburg. »Widespread use in the current outbreak is hardly realistic earlier than mid-2027. In the best case scenario, they will be ready for future outbreaks. The manufacturers announced that they could each provide around half a million doses cost-effectively.

In the case of Ebola, not all people in a region are vaccinated prophylactically. As with Mpox, so-called ring vaccinations of contacts of infected people and their contacts have proven successful. Ebola outbreaks can actually be stopped without vaccines, as was the case with the epidemic in West Africa in 2013-15: with an effective contact tracing system. Although the virus has an extremely high death rate - it is currently around 50 percent in Congo - it does not spread through the air, but only through direct contact with the body fluids of infected people.

However, tracking is currently working at a maximum of 80 percent, as reported from the Congo. And a large proportion of new cases come from completely unknown transmission chains. There are many reasons for this: armed conflicts with numerous militias, the sometimes high mobility of the population and the poorly equipped healthcare system. Many also avoid health centers for fear of infection. All of this is also a disadvantage when using vaccines.

WHO Director-General Tedros Adhanom Ghebreyesus also has to admit this, even though he describes the new vaccines as “proof of the power of science and collaboration.” “Vaccines alone will not end this outbreak,” says Tedros, “but they could become a powerful new tool to bring it under control.” In this respect, the hope associated with the Tumaimi study is more of a glimmer of hope.

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