Dr Betty Mwesigwa was driving to the Makerere University Walter Reed Program (MUWRP) offices in Kampala  in 2022, when a news alert aired on radio. Ministry of Health officials had confirmed an outbreak of the Sudan strain of Ebola in Kassanda and Mubende districts in Central Uganda.

“You can imagine the pain… watching the (last Sudan Ebola virus) outbreak kill 55 people in part because we didn’t have an approved vaccine. We need a vaccine that is safe, cost-effective, and can work for all of us.”

– Betty Mwesigwa, Deputy Executive Director at MUWRP

Immediately, Mwesigwa – who is the Deputy Executive Director at MUWRP – felt anxious: first, because Sudan Ebola virus is one of the deadliest filoviruses, ranking alongside the Marburg virus and the Zaire strain of Ebola, which killed more than 11,000 people in West Africa between 2014 and 2016, and second, because unlike the Zaire strain of the Ebola virus, Sudan Ebola virus didn’t yet have an approved vaccine. 

Moving fast

Mwesigwa needed to do something. MUWRP had partnered with Sabin Vaccine Institute in the US to evaluate an candidate Sudan Ebola virus vaccine in a phase 1 clinical trial that”elicited rapid and robust immune responses” among trial participants. At this early stage, the vaccine’s safety record was reassuring. Might Sabin, Ugandan authorities and the World Health Organization (WHO) consider deploying the investigational vaccine on an emergency basis? She would consult with the rest of the team when she got to the office.

They pushed forward. The vaccine doses were shipped, with Sabin’s vaccine being the first to arrive in Uganda after WHO included it among three vaccines for possible use in an outbreak trial. But the outbreak ended on 11 January, 2023, before the vaccine could roll out.

That didn’t stop Mwesigwa’s team and the Sabin Institute from pushing to take the experimental vaccine to a larger phase 2 trial.

“These filoviruses have shown that they are always re-emerging,” said Mwesigwa in an interview with VaccinesWork.”If you look at our (East African) region in the last decade… we have had Ebola, Crimean–Congo haemorrhagic fever and, most recently, Marburg in Rwanda. So, we still needed a vaccine in case this Sudan Ebola virus re-emerges.”

“We still needed to get back to the clinic, to continue developing a vaccine so when the next outbreak hit, we would be more than ready,” she continued.”You can imagine the pain… watching the (last Sudan Ebola virus) outbreak kill 55 people in part because we didn’t have an approved vaccine. We need a vaccine that is safe, cost-effective, and can work for all of us.”

Putting together phase 2

In May 2024, Sabin dispatched a batch of investigational vaccines for the phase 2 trial to MUWRP and the Kenya Medical Research Institute (KEMRI) in Kenya. After receiving all requisite local ethics and regulatory approvals from the National Council for Science and Technology, MUWRP set about recruiting study participants. Enrolment into the study commenced in July 2024.

Today, the Sudan Ebola virus phase 2 vaccine clinical trial (code-named Sabin 003) has enrolled 125 participants – 62 participants at MUWRP and the rest at KEMRI. Each participant, including younger (18–50 years) and older age groups (51–70 years) has received a single dose of the investigational vaccine. They will be monitored for a full year.

“Participants have to be in good health as determined by the study doctor, including not having infectious diseases and other chronic diseases or conditions,” said Mwesigwa, the study’s principal investigator. They also have to agree to use contraception to avoid getting pregnant during the study, because researchers do not yet know the impact of the experimental vaccine on a foetus.

“It is a randomised, placebo-controlled, double-blind study, meaning that neither the participants nor the study staff know whether trial participants receive a vaccine dose or a placebo dose until after the trial follow-up visits for all participants are concluded. This is to help reduce experimental bias,” she said.

The trial will evaluate the experimental vaccine’s safety and immunogenicity – its ability to induce a specific immune response – among participants.

Amy Finan, Sabin’s Chief Executive Officer, said when she announced the phase 2 trials earlier this year that they were delighted to advance a vaccine candidate that can thwart a”deadly and devastating disease that caused a fairly recent outbreak and for which no approved treatments exist.”

“Sabin’s vaccine candidate is backed by strong safety and immunogenicity data, and we hope this trial will yield further evidence to move the vaccine closer to licensure,” Finan said.

“It’s a positive thing”

Dr Misaki Wayengera, medical researcher and lecturer for pathology, immunology and molecular biology at the College of Health Sciences at Makerere University, commended researchers at Sabin and MUWRP for progressing the investigational vaccine to larger phase 2 trials.

“Sudan Ebola virus, like other filoviruses, belongs to the filoviridae family of single-stranded negative-sense RNA viruses that have historically caused viral haemorrhagic fevers in remote equatorial Africa. But the 2014 outbreak (of Zaire Ebola virus) that spread beyond West Africa to the USA woke up researchers to start developing vaccines to stop these pathogens. That said, we only have approved vaccines for the Zaire Ebola virus strain,” Dr Wayengera explained.

“So, it’s a positive thing that researchers at Sabin and MUWRP are now testing an experimental vaccine for the Sudan Ebola virus strain,” said Wayengera.”Developing these vaccines will help us to contain the virus if and when there is an outbreak. For instance, we can deploy these vaccines among health workers (and most-at-risk-populations) to contain the outbreak.

“Secondly, because of fear, these diseases cause social economic disruptions… We had to close Mubende and Kassanda districts (during the 2022 outbreak in Uganda). A vaccine would help us to mitigate the negative social economic impact that these diseases cause in case of an outbreak,” he said.”Thirdly, having vaccines that work can be a guard against acts of bioterrorism, especially in our East African region that is dogged with terror and conflict.”

“It’s also a positive thing that these vaccines are being tested here… in populations who are at risk and are likely to use these products,” said Wayengera.

Jhalia Nassiwa, who survived the last Sudan Ebola virus outbreak in Kassanda district, welcomed the trials.”I remember when I tested positive (for the virus) and was placed in an isolation ward, I thought I was going to die… I had a headache, diarrhoea, terrible joint and stomach pains. Even after I got discharged, medics advised me to not breastfeed my baby or to engage in unprotected sex for (six months) so that I did not pass on the virus to the child or my sex partner in case I still had it inside of me. So, it is very important that researchers are working on a vaccine to stop this virus.”

Constance Nabatanzi, who lost her brother in the 2022 outbreak, shared the same sentiment.”Vaccines have always helped to boost people’s immunity to fight off diseases, especially when taken early. I think that my big brother would still be alive if we had had vaccines to protect him against that virus in 2022.”

Mwesigwa hopes to conclude the trial in October 2025 wheninterim results are expected.”We still have a long way to go,” she said.”One of the primary objectives of the study is to determine whether the vaccine induces an immune response, which will be assessed through study results. Depending on the results (which have to be good or promising) subsequent trials will need to be conducted to further evaluate the vaccine’s effectiveness.”