Berlin-developed Ebola vaccine heads toward African trial

Why it matters: The Ebola epidemic in the Democratic Republic of the Congo is becoming a stress test for global vaccine preparedness. The outbreak is not being caused by Zaire Ebola virus, for which the approved vaccine Ervebo is already available, but by the much rarer Bundibugyo Ebola virus. There is currently neither an approved vaccine nor a specific treatment for this virus. At the same time, case numbers in the DR Congo continue to rise exponentially.

• According to the WHO, nearly 5,000 people had already been infected and more than 2,300 had died by mid-August. The figures have since risen further, with the epidemic spreading across six provinces and numerous health zones. In mid-August, the WHO explicitly described the situation as “far from being under control.” Conflict, displacement, high population mobility and difficulties with contact tracing are making containment even more challenging.

The big picture: The Minapharm candidate is by no means an isolated project. Under the pressure of the current outbreak, an unusually broad vaccine pipeline has emerged within just a few months. CEPI is now supporting five Bundibugyo-specific candidates. They are based on different technologies — a deliberate portfolio strategy, given the limited amount of available data and the risks of relying on a single platform.

• ChAdOx1 BDBV is one of the most advanced candidates, developed by the University of Oxford and the Serum Institute of India. The adenovirus vector-based vaccine uses the same underlying platform as the Oxford/AstraZeneca COVID-19 vaccine. The first Phase I trial began in Oxford in July and is enrolling 50 healthy adults. In parallel, the Serum Institute produced around 620,000 doses in just two weeks for potential future use.
• rVSVdeltaG-BDBV-GP, a candidate from IAVI and the University of Texas Medical Branch (UTMB), is based on the recombinant vesicular stomatitis virus (rVSV) platform that also underpins the approved Zaire Ebola vaccine Ervebo. Preclinical data suggest that a single dose could provide rapid protection. The WHO had already identified the candidate as particularly promising in May.
• Other platforms are also under development, including an mRNA vaccine from Moderna and, now, the MVA-based approach from Minapharm and ProBioGen. This technological diversity is itself part of the strategy: Established vector platforms benefit from extensive prior experience, while technologies such as mRNA and MVA could allow rapid adaptation and manufacturing. A recent review in npj Vaccines identifies rVSV, ChAdOx1 and mRNA among the prioritized approaches, while other programs are using measles virus or MVA vectors, among others.

Also notable: Paradoxically, an already approved vaccine is nevertheless being used during the current epidemic. The WHO has made 70,000 doses of MSD-developed Ervebo available to the DR Congo, with the first shipments already delivered. However, Ervebo is approved against Zaire Ebola virus, not Bundibugyo. Whether, and to what extent, it protects against the virus responsible for the current outbreak remains unclear.

• The WHO now recommends studying Ervebo in a Phase III trial during the current outbreak. In parallel, CEPI is funding four studies using blood samples from vaccinated people to determine whether existing Zaire Ebola vaccines can induce at least some cross-reactive immune response or provide a degree of protection against Bundibugyo.

Worth watching: The case also illustrates how the logic of vaccine development for emerging pathogens is changing. Through its “100 Days Mission,” CEPI aims to bring vaccines against new epidemic threats into clinical development within roughly 100 days. In the case of Bundibugyo, however, the starting point is not sufficient to fully achieve that goal: Before 2026, the virus had only been associated with a small number of outbreaks, leaving a correspondingly limited clinical evidence base.

• The current response is therefore more of a test of portfolio and platform readiness. Oxford was able to move ChAdOx1 into the clinic relatively quickly because the platform, manufacturing partner and regulatory experience were already in place. IAVI can build on the rVSV technology used for Ervebo. Minapharm and ProBioGen, meanwhile, are contributing an MVA platform as well as manufacturing capacity in Africa.
• That last point could ultimately prove more important than the individual vaccine candidate itself. Minapharm will initially have the active substance manufactured under GMP conditions at ProBioGen in Germany, after which the material will be processed into the finished vaccine in Cairo. The plan is also to transfer active-substance manufacturing to Egypt. The aim is therefore to establish production that is as local and self-contained as possible.

Between the lines: This gives the project an industrial-policy dimension as well. The Ebola crisis highlights how dependent many African countries remain on manufacturing sites outside the continent for vaccines and other medical countermeasures. The Minapharm/ProBioGen approach therefore combines vaccine development, technology transfer and the expansion of African manufacturing capacity.

• This is consistent with the approach increasingly pursued by CEPI and Africa CDC: Epidemic preparedness should not consist solely of sourcing finished vaccines from Europe, the US or Asia once a crisis has begun. Instead, scientific, regulatory and industrial capabilities should already be available on the continent before the next outbreak occurs.
• The current Ebola outbreak also demonstrates the limitations of this strategy. Even if a vaccine candidate enters the clinic within a matter of months, efficacy, regulatory approval and sufficient manufacturing volumes are by no means guaranteed. The critical gap lies between being “clinically ready” and being genuinely available during an outbreak.

Yes, but: For the global vaccine industry, Bundibugyo therefore provides an interesting counterpoint to the COVID-19 experience. During the pandemic, developers were able to draw on platform technologies built over decades, enormous investment and a huge commercial market. With rare pathogens such as Bundibugyo, by contrast, there is little commercial incentive to develop and stockpile vaccines long before an outbreak occurs.

• This is precisely where organizations such as CEPI come in: They finance candidates and platforms before a conventional market exists. The fact that several technologies are now being pursued in parallel is less a sign of inefficiency than of risk management. The more independent programs there are, the greater the likelihood that at least one approach will be able to demonstrate safety, immunogenicity, efficacy and manufacturing readiness quickly enough.

Bottom line: The Ebola outbreak in the Congo offers a sobering but important demonstration of the logic behind pandemic prevention: Vaccine preparedness cannot begin only once an epidemic is already underway. The current race may help narrow the existing gap but closing it will require vaccine platforms, manufacturing capacity, clinical trial infrastructure and financing to remain in a state of standby readiness, much like cars waiting at a traffic light. When a threat emerges, the system should only need to switch to a vaccine adapted to the pathogen and ramp up production capacity.

• Many pandemic-preparedness projects already rehearse such processes theoretically, almost like a dry run. Whether the funding currently allocated to these initiatives is sufficient to maintain them sustainably remains very much open to question. What all stakeholders should recognize, however, is that the savings generated by preventing the pandemic-scale spread of emerging infectious diseases at an early stage — or preventing known infections from spreading far beyond their usual regional boundaries — are likely to be substantially greater than the cost of maintaining laboratory and manufacturing capacity in readiness.