Development of Ebola vaccines

Ebola virus disease (EVD), formerly known as Ebola hemorrhagic fever, is a rare and deadly disease caused by infection with one of the Ebola virus strains. EVD outbreaks have occurred sporadically in Africa since 1976. The largest outbreak in history of EVD occurred in West Africa from 2014 to 2016. Over 28,000 cases and 11,000 deaths were reported. This unprecedented outbreak highlighted the need for an approved vaccine against EVD. Several vaccine candidates entered clinical trials rapidly to evaluate their safety and efficacy.

Early Vaccine Candidates
Some of the earliest vaccine candidates evaluated included viral vectored vaccines and DNA vaccines. A viral vectored vaccine called VSV-EBOV was one of the first vaccine candidates to enter human trials in 2015. It uses an engineered vesicular stomatitis virus (VSV) that produces an Ebola virus protein. Phase 1 and 2 trials demonstrated 100% efficacy with a single dose. Side effects were generally mild.

Another front runner was a two-dose DNA vaccine called TKMEBOV. It uses DNA plasmids encoding Ebola virus proteins. Phase 1 and 2 trials showed the vaccine was generally well tolerated and induced antibody responses. However, its efficacy could not be conclusively determined before the outbreak ended. Both VSV-EBOV and TKMEBOV laid the foundation for further vaccine development by demonstrating acceptable safety profiles.

Regulatory Approval of rVSV-ZEBOV
As the West Africa outbreak wound down, one vaccine candidate stood out - an engineered live-attenuated vesicular stomatitis virus known as rVSV-ZEBOV. It was initially developed by the Public Health Agency of Canada and licensed to Merck and others for further development and use. Additional efficacy data collected during the outbreak confirmed rVSV-ZEBOV provided nearly 100% protection against EVD with a single dose. Its safety profile also proved favorable.

Based on these results, rVSV-ZEBOV received regulatory approval from the European Medicines Agency in July 2019 under the trade name Ervebo. It was approved for indications of active immunization in individuals aged 18 years or older at risk of Ebola virus infection. Subsequently, it was granted approval by the U.S. Food and Drug Administration in December 2019, making it the first FDA-approved Ebola vaccine. It signified a major milestone in Ebola virus prevention.

Stockpiling and Use of Ervebo
Following regulatory approvals, production of Ervebo was scaled up by Merck to meet global demand. The World Health Organization (WHO) worked with countries and organizations to establish an Ervebo stockpile for emergency response against future outbreaks. Dosing guidance was also developed for using Ervebo during outbreaks.

The stockpile was put to test during the 2018-2020 Ebola outbreak in the Democratic Republic of Congo, the second largest on record. Frontline healthcare workers were prioritized for vaccination with Ervebo to protect them while they cared for patients. Over 300,000 doses were deployed from the stockpile and ring vaccination strategy was employed to contain the spread. Preliminary analyses showed Ervebo effectively protected recipients against the virus, thereby curbing the outbreak. Its use highlighted the crucial role vaccines can play against deadly diseases even in challenging environments like conflict zones.

Ongoing Developments
While Ervebo provides a powerful tool against Ebola, research into new and improved vaccines still continues. Multiple clinical studies are ongoing to evaluate different vaccine candidates and regimens that may offer longer lasting immunity with fewer doses. Second generation vaccines under development include additional VSV vectored vaccines, adenovirus vectored vaccines, subunit vaccines and others. Some candidates aim to be effective against all four commercially relevant species of the Ebola virus.

Partner organizations like WHO, Coalition for Epidemic Preparedness Innovations (CEPI) and others continue stockpiling Ervebo as well as supporting further research. The goal is to eventually replace Ervebo with more easily administered second generation vaccines offering longer protection. Development is also continuing on therapeutics and rapid diagnostic tests to complement Ebola prevention and response capabilities. By pairing vaccines, drugs and diagnostics, public health officials hope to minimize future Ebola outbreaks and their damaging impact on global health security.

Development of the Ebola vaccine Ervebo within a record short timeframe represented a major breakthrough in the medical response against the deadly Ebola virus. Approval and stockpiling enabled its deployment during current and future outbreaks, protecting frontline responders and helping contain transmission. While work still continues towards improved vaccines, available data confirms the successful use of the pioneering Ervebo vaccine in curtailing outbreaks and saving lives. Its approval demonstrated what international cooperation and commitment can achieve during health emergencies through accelerated research and approvals. Ebola prevention capabilities have been significantly strengthened but continued vigilance and preparation remains essential against this unpredictable yet potentially devastating disease. 

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