Moderna, best known for its mRNA COVID vaccine, is development an experimental mRNA vaccine against rare species of Bundibugyo virus behind the ongoing Ebola outbreak in the Democratic Republic of Congo and Uganda, with support of up to $50 million 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 program was designed to move forward with urgency,” Moderna said in a statement shared with Scientific American. The company said it is working to accelerate the candidate’s move to a Phase 1 clinical trial (an early-phase safety trial) “in the coming months,” subject to regulatory review and approvals.
This effort is part of a broader initiative to fill one of the gaps revealed by the epidemic: vaccines against Ebola exist. but not for all species of the Ebola virus which can cause fatal diseases in humans.
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Acceleration of processing of three vaccine candidates
I caught committed up to $60 million in funding to develop three Bundibugyo vaccine candidates: Moderna’s mRNA vaccine, an IAVI (formerly International AIDS Vaccine Initiative) candidate, and an Oxford University candidate to be manufactured by the Serum Institute of India. Each uses a different proven technology. mRNA uses genetic instructions to cause the body to produce a viral protein; The IAVI vaccine candidate uses a recombinant vesicular stomatitis virus, a weakened version of a virus capable of infecting 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, deputy executive director of CEPI, says the organization acted quickly because the outbreak is “deeply concerning” and no approved vaccine is available. CEPI mobilized resources a little more than two weeks after the DRC announced the outbreak in mid-May, she says, to come up with vaccine candidates that could help control the outbreak. 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 affected countries, Nguyen said. “Having multiple shots on goal increases our chances of developing an effective vaccine,” says Nguyen.
For Moderna, CEPI 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 is promising.
For IAVI I caught it committed up to $3.2 million in initial funding for work to prepare a virus master seed stock, a raw material for vaccine manufacturing. For Oxford and the Serum Institute of India, CEPI promised up to $8.6 million for preclinical testing, vaccine development and manufacturing of clinical-grade doses.
If the initial trials are successful, Nguyen says, CEPI hopes to work with partners to support late-stage trials that could generate data allowing regulatory agencies to issue an emergency use authorization or operating permit.
Why Bundibugyo was left behind
Scientists Bundibugyo virus identified for the first time 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 outbreak in West Africa and several subsequent outbreaks in the DRC.
This history has shaped vaccine development. Most Ebola control work has focused on the Ebola virus, which has caused larger outbreaks than Bundibugyo and has also been treated as a potential biological warfare threat. The licensee Ebola vaccine Ervebo is approved for Ebola virus, not Bundibugyo virus.
Amesh Adalja, a senior scholar at the Johns Hopkins Center for Health Security, says the current outbreak shows what the consequences of this narrower focus have been and why rarer species of Ebola cannot be ignored. Although Bundibugyo has historically been a lower priority because it has caused fewer known outbreaks, “these are all deadly diseases. They all deserve some level of attention,” he says.
Nguyen says CEPI’s investments before this outbreak had also focused on members of the filovirus family (the family that contains orthoebolaviruses and related viruses) deemed to pose greater epidemic risk and lacking sufficient countermeasures, including Ebola virus, Marburg virus, and Soudan virus, another orthoebolavirus. Since the Ebola virus was identified in 1976, she said, there have been more than 50 outbreaks of different filoviruses, but Bundibugyo had only caused two before the current outbreak.
Before funding Bundibugyo vaccine candidates, she said, CEPI had already begun investing in broader “all-in-one” vaccines that could potentially provide protection against a range of filoviruses, including Bundibugyo. These programs are still in their early stages, but CEPI is evaluating whether any of these vaccine models could be tested during the current outbreak.
Consider mRNA Vaccines
The outbreak has renewed attention on whether mRNA technology can help public health systems better prepare for outbreaks of rarer species of Ebola.
Moderna said its candidate Bundibugyo builds on more than a decade of research on the mRNA platform and years of work to design mRNA vaccines against filoviruses. As soon as the relevant genetic sequence of the Bundibugyo Ebola virus became availableAccording to the company, it was able to “design and quickly 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 modify the genetic sequence encoded by the vaccine. Nguyen says the Moderna platform provides genetic instructions for the Bundibugyo glycoprotein, a protein molecule 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 contained in the vaccine. This flexibility, Moderna said, can reduce the time needed to design and produce a vaccine candidate.
Adalja says mRNA vaccines may not be the best vaccine technology for all pathogens, but their speed makes them important for emerging threats.
The COVID pandemic has changed the way vaccines are developed during an outbreak, Nguyen says. This not only provided an opportunity to validate mRNA and other adaptable vaccine platforms, but also enabled the broader vaccine development chain to be more quickly activated in the event of an outbreak. The three Bundibugyo vaccine technologies funded by CEPI use validated platforms, approved vaccine bases or established manufacturing processes that can be adapted to different pathogens, she says.
Compared to the first COVID response, Nguyen says, coordination has also progressed more quickly. Global health officials met less than a week after the current Ebola outbreak was declared and African research and leadership played a central role in the response, she said.
What speed can’t solve
Even with faster platforms, vaccine development is still not instantaneous.
Moderna said its mRNA system can accelerate 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, human safety evaluations, immune response studies, regulatory reviews, clinical trial site evaluation, ethical approvals and data generation for any emergency use or licensure proceedings.
Nguyen says vaccine development remains complex, even when the steps happen in parallel. Technical obstacles may arise, including problems producing test materials or unexpected safety signals in studies. Field trials in eastern DRC could also be complicated by geopolitical conflict, weak health systems, misinformation and population movements, which could affect recruitment and data collection.
Moderna did not give a firm timeline for these trials, only indicating that it is working on phase 1 tests 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 outbreak.
“Even if the candidate is not available in time to materially affect the current outbreak, its advancement could significantly strengthen preparedness for future Bundibugyo Ebola virus outbreaks,” Moderna said.