Global health authorities are urgently seeking medical solutions to combat an Ebola outbreak in the eastern Democratic Republic of Congo, linked to the Bundibugyo strain of the virus.
Unlike the more common Zaire strain, for which approved vaccines and treatments exist, there are currently no specific medical interventions for Bundibugyo.
The current outbreak is believed to have caused about 906 cases and 223 suspected deaths in the DRC, with the World Health Organisation (WHO) warning that these figures are likely to increase.
The Bundibugyo ebolavirus (BDBV) carries a significant fatality rate, reaching up to 40 per cent.
A limited number of experimental vaccines and therapies are under evaluation, while global health bodies are also investigating whether any existing Ebola treatments could offer protection, though current evidence is restricted to animal studies.
Most of these experimental options have not yet undergone human trials, necessitating emergency or compassionate-use authorisation before they can be deployed in Congo.
The WHO recently advised prioritising several experimental drugs, including antibodies, antivirals, and vaccines, for both the treatment and prevention of BDBV.
Here is what we know of these candidates so far:
Ebola vaccines
1. The WHO said on Thursday a single-dose rVSV Bundibugyo vaccine being developed by the International AIDS Vaccine Initiative is the most promising candidate to prevent BDBV.
The vaccine, rVSVΔG/BDBV-GP, which uses the same technology as Merck’s MRK.N approved vaccine Ervebo for the Zaire strain, has shown survival benefit in non-human primates in a 2023 proof-of-concept study.
The WHO said development of the vaccine would likely take seven to nine months before it is ready for assessment in a clinical trial.
The International AIDS Vaccine Initiative said it is advancing the candidate towards a clinical trial and preparing for manufacturing, including transferring the vaccine virus and processes for Good Manufacturing Practices production.
2. The WHO has recommended prioritising another vaccine candidate, ChAdOx1 Bundibugyo, being developed by Oxford University and the Serum Institute of India.
The potential vaccine is based on ChAdOx1 technology, which was used in the Oxford/AstraZeneca AZN.L COVID-19 vaccine, and is being manufactured by the Serum Institute.
The company started production under its “emergency response framework”, alongside partners Coalition for Epidemic Preparedness Innovations, or CEPI, and the University of Oxford, as soon as it got word of the outbreak this month, a spokesperson said.
Doses could be ready within two to three months for efficacy assessment through a clinical trial, the WHO said, adding that additional animal studies have yet to be conducted.
The WHO said experts considered a single dose of the vaccine candidate potentially suitable for contacts of Ebola cases, while a two-dose regimen might be used for high-risk but unexposed groups, including healthcare workers and frontline responders.
The Oxford Vaccine Group said it is working to generate pre-clinical data to support the development and testing of the ChAdOx1 BDBV vaccine.
CEPI, which funded some of the early COVID-19 vaccines and aims to have shots available within 100 days of an outbreak, said it is in talks with both candidates about how to speed up development.
Antibody drugs
1. The WHO has recommended prioritising privately held Mapp Biopharmaceutical’s pan-ebolavirus antibody drug, MBP134 – a combination of two human monoclonal antibodies – for clinical trials among confirmed BDBV cases.
Initially studied for the Sudan ebolavirus strain, the drug was found to be safe and well tolerated in early-stage trials. Development has been backed by the U.S. Biomedical Advanced Research and Development Authority, or BARDA.
BARDA said it is coordinating shipments of the investigational treatment for potential use in high-risk Americans exposed to the virus.
Mapp said MBP134 has shown similar activity against all known ebolaviruses and that it is working with the WHO and other authorities as part of the response to the Congo outbreak.
2. Regeneron Pharmaceuticals’ REGN.O antibody drug candidate, maftivimab, is also being explored as a potential treatment by the WHO. According to the company, it has been shown in a lab to be active against the Bundibugyo Ebolavirus.
Regeneron said it is working to prepare existing supply of maftivimab for use in upcoming clinical trials.
The FDA has approved a combination of maftivimab and two other antibodies, atoltivimab and odesivimab, under the brand name Inmazeb, to treat Zaire Ebolavirus infection in adult and pediatric patients.
The company said it recently donated 500 doses of Inmazeb to the WHO, which could be used if found helpful.
“Supply of Inmazeb is already on the ground in the DRC, should WHO wish to utilize it for immediate treatment or as an additional component of the study,” Regeneron said.
3. Human monoclonal antibodies isolated from Bundibugyo survivors have also been explored as potential treatments.
One candidate, BDBV289-N, demonstrated efficacy in a 2018 animal study. The study, conducted by a group of researchers with support from the U.S. National Institutes of Health, showed the antibody gave up to 100% protection in infected monkeys, even when treatment started up to eight days after the infection.
Antiviral drugs
Gilead Sciences’ GILD.O experimental oral antiviral drug obeldesivir is being considered as a potential post-exposure treatment by the WHO to prevent those exposed to Ebola from developing the disease.
Once-daily obeldesivir given for 10 days provided up to 100 per cent protection in monkeys against the Zaire and Sudan Ebola strains when treatment began 24 hours after exposure.
“Obeldesivir is predicted to be active against this particular (Bundibugyo) strain. While not approved for this, we do have preclinical data that shows positive results,” a company spokesperson said.
Gilead’s antiviral remdesivir has shown activity against the Bundibugyo virus in laboratory studies conducted by researchers at the University of Texas Medical Branch. Some data suggest the drug, given as an intravenous infusion, may have stronger activity against BDBV than against the Zaire Ebola strain.
The WHO has also recommended a combination therapy using a monoclonal antibody and remdesivir for evaluation.
Tests
The WHO had indicated that limited testing capacity for the Bundibugyo strain was slowing response to the outbreak. Here are tests that can detect the infection.
- BioFire Defense, an affiliate of French diagnostic firm bioMérieux BIOX.PA, makes an FDA-cleared test – BioFire Global Fever Special Pathogens Panel – that can detect multiple Ebola species, including Bundibugyo. A company spokesperson said it is increasing production capacity and engaging with public health stakeholders and international contacts to assess potential needs.
- Germany-based firm Altona Diagnostics’ test, called RealStar Filovirus Screen RT-PCR Kit 1.0, is being used to detect the Bundibugyo outbreak in Congo. The firm has ramped up production to support local testing facilities in Congo.
