The large and deadly epidemic of Ebola caused by Bundibugyo virus in the Democratic Republic of Congo and Uganda has exposed critical gaps in the world’s defences against this deadly infectious disease: there are currently no licensed vaccines or treatments designed specifically to target the Bundibugyo species of Ebola.
CEPI has activated its highest level of response and moved immediately to identify a number of candidate vaccines to be developed and advanced into human trials to assess their potential against Bundibugyo virus.
The first candidates in CEPI’s Bundibugyo portfolio use distinct vaccine platforms, or delivery systems, which will be paired with key bits of Bundibugyo virus to teach the body’s immune system to recognise and fight against infection.
As work on these candidates begins, CEPI is also assessing other potentially promising options, including through an openCall for Proposals.
Why is CEPI funding multiple different projects?
Since no single vaccine development approach is guaranteed to succeed, CEPI’s portfolio approach is designed to spread the risk and to maximise both speed and the chance that one or more of the candidates will prove effective in human trials.
This is a real-time practical application of components of CEPI’s 100 Days Mission: using pre-designed and well-established vaccine platforms, partnerships and networks to move as quickly as possible when a life-threatening new epidemic erupts.
These three platforms have extensive safety data and prior preclinical or clinical efficacy data with other viruses in the same Filovirus family as Bundibugyo, including Zaire Ebola, Sudan virus and Marburg virus.
Three potential paths to an effective Bundibugyo Ebola vaccine
- VSV viral vector
The first approach is based on the same vaccine platform which was used to develop the highly effective licensed vaccine against Zaire Ebola. It uses a recombinant vesicular stomatitis virus (VSV) as a viral vector vaccine platform. This harmless, modified virus is engineered to display the Bundibugyo glycoprotein to the immune system.
This approach is important because at this stage it has the strongest existing preclinical evidence among the three options. However, no Bundibugyo-specific VSV vaccine has yet been tested in people. The immediate priority is to prepare for manufacturing by generating a Master Virus Seed stock - the starting material needed to manufacture a vaccine - so the candidate can advance towards potential clinical evaluation.
- ChAdOx viral vector
The second approach uses a ChAdOx viral vector platform – the same technology that underpinned the Oxford/AstraZeneca COVID-19 vaccine. It offers strong potential for rapid manufacturing and scale-up, an important advantage in an outbreak setting. But this speed comes with some uncertainty. There is currently very limited Bundibugyo-specific preclinical data for this construct, and key studies are currently under way.
- mRNA platform:
The third approach uses an mRNA platform, which delivers genetic instructions encoding the Bundibugyo glycoprotein. Rather than introducing a viral vector, this approach uses a synthetic molecule known as messenger RNA to tell the body’s own cells to produce the antigen.
mRNA platforms were validated during the COVID-19 pandemic as safe, fast, flexible, scalable vaccine technology.
If early-stage testing of this candidate proves promising, it offers the potential for a very rapid path from vaccine design to manufacturing. However, as with the ChAdOx platform, there is very limited data for this platform with Bundibugyo virus specifically, so the immediate focus is on generating important early data at the same time as preparing for rapid progression if early preclinical test results look promising.
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