Moderna, best known for its COVID mRNA vaccine, is developing an investigational mRNA vaccine against the rare Bundibugyo virus species driving the ongoing Ebola outbreak in the Democratic Republic of the Congo and Uganda with up to $50 million in support from the Coalition for Epidemic Preparedness Innovations (CEPI). The effort could move the candidate toward early human trials within months, the company and CEPI say.
“The programme has been designed to move with urgency,” Moderna said in a statement shared with Scientific American. The company said it is working to accelerate the candidate into a phase 1 clinical trial (an early phase safety trial) “in the coming months,” subject to regulatory review and approvals.
The effort is part of a wider push to close one of the gaps exposed by the outbreak: Ebola vaccines exist but not for every species of Ebola virus that can cause deadly disease in humans.
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Fast-Tracking Three Vaccine Candidates
CEPI has committed up to $60 million in funding to develop three Bundibugyo vaccine candidates: Moderna’s mRNA vaccine, a candidate from IAVI (formerly the International AIDS Vaccine Initiative), and a University of Oxford candidate that will be manufactured by the Serum Institute of India. Each uses a different proven technology. mRNA uses genetic instructions to make the body produce a viral protein; the IAVI vaccine candidate uses a recombinant vesicular stomatitis virus, a weakened version of a virus that can infect livestock, as a vector to deliver genetic instructions for a Bundibugyo virus protein. And Oxford’s ChAdOx platform uses a modified chimpanzee adenovirus as a delivery vehicle.
Aurélia Nguyen, CEPI’s deputy CEO, says the organization moved quickly because the outbreak is “deeply concerning” and no approved vaccine is available. CEPI mobilized resources just over two weeks after the DRC announced the outbreak in mid-May, she says, to advance vaccine candidates that could help control the epidemic. CEPI selected the three candidates after a global review and consultations with the World Health Organization, the Africa Centers for Disease Control and Prevention, Gavi, the Vaccine Alliance, and the affected countries, Nguyen says. “Having multiple shots on goal increases our chances of developing a successful vaccine,” Nguyen says.
For Moderna, CEPI’s support will fund preclinical testing and a phase 1 clinical trial. The funding will also allow the company to manufacture doses of its vaccine in parallel so that larger phase 2/3 trials can begin quickly if phase 1 data are promising.
For IAVI, CEPI has committed up to $3.2 million in initial funding for work needed to prepare a master virus seed stock, a starting material for vaccine manufacturing. For Oxford and the Serum Institute of India, CEPI has promised up to $8.6 million for preclinical testing, vaccine development and manufacturing of clinical-grade doses.
If early trials are successful, Nguyen says, CEPI expects to work with partners to support late-stage trials that could generate data for regulatory agencies to issue an emergency use authorization or licensure.
Why Bundibugyo Was Left Behind
Scientists first identified Bundibugyo virus in Uganda in 2007, but the species has caused far fewer known Ebola outbreaks than the original Ebola virus (formerly Zaire virus), the species responsible for the devastating 2013 to 2016 West African epidemic and several later outbreaks in the DRC.
That history shaped vaccine development. Most Ebola countermeasure work has focused on the Ebola virus, which has caused larger outbreaks than Bundibugyo and was also treated as a potential biological warfare threat. The licensed Ebola vaccine Ervebo is approved for the Ebola virus, not Bundibugyo virus.
Amesh Adalja, a senior scholar at the Johns Hopkins Center for Health Security, says the current outbreak shows what consequences of that narrower focus have been and why rarer Ebola species cannot be ignored. Though Bundibugyo has historically been a lower priority because it has caused fewer known outbreaks, “all of these are deadly diseases. All of these deserve some level of attention,” he says.
Nguyen says CEPI’s investments before this outbreak had similarly focused on members of the filovirus family (the family that contains orthoebolaviruses and related viruses) judged to pose greater epidemic risk and lacking sufficient countermeasures, including Ebola virus, Marburg virus and Sudan virus, another orthoebolavirus. Since Ebola virus was identified in 1976, she says, there have been more than 50 outbreaks of different filoviruses, but Bundibugyo had caused only two before the current outbreak.
Prior to funding Bundibugyo vaccine candidates, she says, CEPI had already begun investing in broader “all-in-one” vaccines that could potentially provide protection across a range of filoviruses, including Bundibugyo. Those programs remain at an early stage, but CEPI is assessing whether any of these vaccine designs could be tested during the current outbreak.
Considering mRNA Vaccines
The outbreak has renewed attention on whether mRNA technology can help public health systems be better prepared for outbreaks of rarer Ebola species.
Moderna said its Bundibugyo candidate builds on more than a decade of mRNA platform research and years of work designing mRNA vaccines against filoviruses. As soon as the relevant Bundibugyo ebolavirus genetic sequence became available, the company said, it was able to “rapidly design and begin developing multiple vaccine candidates” using its established platform.
The advantage of mRNA is that the underlying platform can remain largely the same while researchers change the genetic sequence encoded by the vaccine. Nguyen says the Moderna platform delivers genetic instructions for the Bundibugyo glycoprotein—a protein molecule found on the virus—that tells the body’s own cells to produce it.
mRNA vaccines do not require manufacturers to grow large quantities of live virus. Instead the same basic production system can be adapted for different vaccines by changing the genetic instructions the vaccine carries. That flexibility, Moderna said, can shorten the time needed to design and produce a candidate vaccine.
Adalja says mRNA vaccines may not be the best vaccine technology for every pathogen, but their speed makes them important for emerging threats.
The COVID pandemic changed the way vaccines are developed during an outbreak, Nguyen says. It not only provided an opportunity to validate mRNA and other adaptable vaccine platforms but also allowed the wider vaccine-development chain to be activated more quickly during an outbreak. All three Bundibugyo vaccine technologies that CEPI is funding use validated platforms, approved vaccine backbones or established manufacturing processes that can be adapted to different pathogens, she says.
Compared with the early COVID response, Nguyen says, coordination has also moved faster. Global health principals convened less than a week after the current Ebola outbreak was declared and African research and leadership have been central to the response, she says.
What Speed Cannot Solve
Even with faster platforms, vaccine development is still not instantaneous.
Moderna said its mRNA system can speed up early vaccine development because the basic design and manufacturing process can be reused, while the genetic instructions inside the vaccine are changed to match a new virus. But, the company said, key steps still require time and cannot be bypassed. These include preclinical studies, safety evaluation in humans, immune-response studies, regulatory review, evaluation of clinical trial sites, ethical approvals and data generation for any emergency-use or licensure pathway.
Nguyen says vaccine development remains complex, even when stages are run in parallel. Technical hurdles can arise, including problems producing trial materials or unexpected safety signals in studies. Field trials in the eastern DRC could also be complicated by geopolitical conflict, weak health systems, misinformation and population movement, which could affect recruitment and data collection.
Moderna has not given a firm timeline for these trials beyond saying it is working toward phase 1 testing in the coming months. Whether the company’s vaccine candidate will be deployed in response to the current Ebola outbreak will depend on the pace of development, emerging data, regulatory pathways and the operational realities of conducting studies and deploying vaccines during an epidemic.
“Even if the candidate is not available in time to materially affect the current outbreak, advancing it could substantially strengthen preparedness for future Bundibugyo ebolavirus outbreaks,” Moderna said.
