The current ebolavirus outbreak in Uganda worries experts. But: In an unexpected turn of events, pharma giant Merck found a viable vaccine candidate in its freezers. Could it help contain the deadly virus?
The current ebolavirus outbreak in Uganda continues. While the first case in the East African country was already reported on September 19th, case numbers have increased to at least 130 infections, 43 of which ended deadly. By now, the virus has reached the densely populated Ugandan capital Kampala – at least 17 cases have been confirmed so far. While these numbers may not be particularly alarming yet, experts agree that a close eye needs to be kept on the further development. Especially the cases in the capital are of concern, as its highly mobile population might accelerate the spread.
“The situation in Uganda is not yet alarming, but it is getting worse. […] The task now is to detect any outbreak quickly and to find the suspected and sick cases and then, of course, to treat them – as best we can – in well-equipped clinics. Not much more can be done at the moment. The virus is now showing up in many parts of the country, so it is not possible to quarantine the whole country”, explains Prof. Peter Kremsner, director of the Institute for Tropical Medicine, Travel Medicine and Human Parasitology at the University Hospital Tübingen. “No one can say what is likely to happen next. No one knows if the whole thing will explode, resolve itself, or ripple along, but that would also mean several hundred, if not thousands, of cases.”
Speaking of ebolavirus, the 2014/2015 outbreak in West Africa comes to mind, which went down in history as the worst Ebola epidemic since the discovery of the virus. More than 11 300 people lost their life to the epidemic. The current situation is different, though, as Prof Roman Wölfel, Col. and Head of the Bundeswehr Institute of Microbiology and associate professor at the Technical University Munich points out. “In contrast to the outbreak in West Africa in 2014, this is not the first time Ebola has occurred in Uganda.” Outbreaks already occurred in 2000, 2007, 2011 and 2018 – in part with the same virus variant that is spreading today. “This is therefore not the first time Ugandan health authorities have faced this highly contagious disease. This is a significant difference from the situation in West Africa, where Ebola did not occur before 2013.” This means that the current containment strategies have already proven their worth and diagnostic capabilities for the virus are readily available. Wölfel continues: “For containment efforts, this can make a big difference […]. This is particularly important in light of the first cases in the megacity of Kampala. The faster containment measures take effect here, the faster this outbreak will be brought under control.”
Nevertheless Kremsner adds: ”All African countries are very well sensitized to such outbreaks because of past Ebola epidemics. But that doesn't mean that outbreak scenarios are also regularly rehearsed on the ground. In addition, the quality of the healthcare system in Uganda is unfortunately far from that in Europe. This can quickly lead to a medical bottleneck as the number of cases increases. The treatment and isolation of Ebola patients is very costly. Therefore, it doesn't take many thousands of cases to potentially overburden Uganda's health care system.”
Therefore, additional weapons to combat the outbreak might be needed – namely vaccines. While well-tried and authorized vaccines against ebolaviruses do exist (Ervebo®), they are not expected to be effective in this situation. The problem lies in the virus strain: What is currently spreading in Uganda is the Sudan strain of the virus, whereas the last big outbreak in West Africa was caused by a different strain, the Zaire strain. Both variants cause the same symptoms (fever, limb pain, vomitus, diarrhea) and are similarly dangerous due to their high mortality rates. Wölfel explains: “The Ebola vaccines approved to date have been developed specifically against the Ebola Zaire virus. Unfortunately, the various viruses in the Ebola virus family do differ more from each other. Therefore, vaccine protection against Ebola-Zaire does not protect against an Ebola-Sudan virus infection […].” While another vaccine (Zabdeno® /Mvabea®) also offers a certain protection against the Ebola-Sudan virus, it requires a special second vaccination against this specific virus strain. “Since eight weeks must elapse between the first and second vaccination, this concept is not suitable for rapid containment, as is now needed in Uganda.”
Now the company Merck raised hopes when they announced that they located a big batch of an experimental vaccine specifically against the Sudan-strain in their freezers in Pennsylvania. The frozen batch might yield about 100 000 doses, which are to be donated to the global nonprofit scientific research organization IAVI for further clinical research use as part of the WHO’s efforts to fight the current outbreak. Merck anticipates that it will be able to deliver approximately 50 000 doses by the end of 2022; WHO and the Ugandan government are now assessing whether and how these doses can be incorporated into clinical trials of two other Ebola vaccine candidates that could launch as soon as next month.
Merck’s vaccine was produced back in 2015/2016 as a side product of the development of the vaccine against the Zaire-strain. It uses a vesicular stomatitis virus (VSV) as a vector – a livestock pathogen that rarely causes harm in humans – which includes a gene for the surface protein of the Sudan ebolavirus, and thus uses the same concept as the already approved Ebola-Zaire-vaccine. “The concept of such a vaccine, which is based on the vesicular stomatitis virus, has proven itself many times. So, in my view, it is also very promising against the Ebola-Sudan virus”, Wölfel states.
However, we must not rejoice too soon. So far, the vaccine has not seen any human trials as there have been no Sudan ebolavirus epidemics since its development. As Kremsner points out, it has merely been tested on monkeys so far, and these results do not necessarily translate into humans. “It is now important to quickly start several phase 1 trials in humans, preferably in Uganda, with the available vaccine candidates. Such studies are possible within a short period of time if the regulatory authority deems the preclinical trials to be sufficient. These will reveal much more than animal trials.”
The two other vaccine candidates are produced by the Sabin Vaccine Institute and the University of Oxford. In contrast to Merck’s vaccine candidate, they are based on a chimpanzee adenovirus as a viral vector.
Image source: Enrico Mantegazza, unsplash
