History of Ebola Vaccine Development
The Ebola virus was first discovered in 1976 during two simultaneous outbreaks in Sudan and the Democratic Republic of the Congo (DRC). Since then, sporadic outbreaks have occurred across Africa, however the largest and most widespread outbreak to date started in West Africa in 2014. This outbreak highlighted the urgency for a licensed Ebola vaccine. Several vaccine candidates entered clinical trials extremely rapidly in response to the epidemic.
Early Vaccine Candidates
Some of the earliest Ebola Vaccine candidates included viruses that were attenuated or weakened versions of the virus, as well as viral-vectored vaccines which used other viruses to deliver Ebola proteins. While these early candidates showed promise in nonhuman primates, further development was limited due to safety concerns for human use. One attenuated virus vaccine called TC-83 was tested in humans in 1987 and showed good protection, but follow up trials did not continue due to the rarity of outbreaks at that time.
mRNA Vaccine Development
With the large 2014-2016 outbreak, new vaccine technologies gained momentum. One promising approach involved mRNA vaccines. These vaccines deliver genetic material into cells that codes for specific Ebola proteins. The cells then produce these viral proteins to induce an immune response without an infectious agent. In 2016, the US National Institutes of Health awarded funding to develop four mRNA Ebola vaccines. Two of these vaccines, one produced by Pfizer and one by Moderna, entered human trials extremely rapidly during the outbreak. Both showed strong immune responses and safety.
Major Trials and Approvals
One of the largest and most important trials of an Ebola vaccine was the "Ring Vaccination Trial" conducted during the 2014-2016 outbreak. This trial tested the rVSV-ZEBOV vaccine, which uses the live vesicular stomatitis virus to deliver an Ebola glycoprotein. The trial demonstrated nearly 100% efficacy in preventing Ebola. Based on these results, the vaccine received regulatory approval in several countries and the WHO recommended its use. In 2019, Merck's rVSV-ZEBOV vaccine, now called Ervebo, received formal approval from the European Medicines Agency and the US Food and Drug Administration, making it the first licensed Ebola vaccine.
Ongoing Developments
While the rVSV-ZEBOV vaccine is now licensed for use during outbreaks, researchers continue developing next generation Ebola vaccines with improved safety and efficacy profiles. The Ad26.ZEBOV/MVA-BN-Filo vaccine developed by Johnson & Johnson recently completed a large phase 3 efficacy study. Early results suggest around 97% efficacy, which would make it an excellent alternative or addition to the current vaccine choices. Ongoing research also aims to develop combination vaccines against multiple viral hemorrhagic fevers like Ebola, Marburg, Lassa and others. Scientists also work on thermostable vaccines that do not require cold chain storage, facilitating distribution in remote areas. Additional vaccines using different platforms continue progressing through clinical trials. With ongoing research efforts, the goal of developing a long-lasting vaccine to prevent future Ebola epidemics moves ever closer.
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